Emanuele RinninellapersName, Pauline RaoulpersName, Marco CintonipersName, Francesco FranceschipersName, Giacinto Abele Donato MiggianopersName, Antonio GasbarrinipersName, Maria Cristina MelepersName (2019date). “What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases.” Microorganismstitle·venue.
Object of study — the composition of the healthy human gut microbiotaterm, and whether a single optimal one exists
Research question — what would be the optimal gut microbiotaterm composition for maintaining immune and metabolic function
Contribution — a reviewterm·mth named after a question about a norm, which answers it in the negative: richness and diversityterm characterise a healthy composition, but the optimal composition is different for every individual
Cross-disciplinary analysis
content-tags & facets:
phenomenon · claim-type · cross-domain-transfer · mechanism · claim-relation · replication-status · limitation — grounded in the full text| phenomenon | gut microbiota composition varies within one person over life and between people, while its FUNCTIONS are highly preserved across people — “It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life.” | |
| claim-type | existence — “These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual.” | |
| method — evidence | — “The majority of these techniques are based on the extraction of DNA and the amplification of the 16S ribosomal RNA gene (rRNA) [5, 6]. 16S rRNA sequencing has become the most useful technique to highlight diversity and abundance of the microbiome.” | |
| object of study — evidence | — “This review aims to define what would be the optimal gut microbiota composition in order to maintain these optimal microbiota immune and metabolic functions.” | |
| research question — evidence | — “This review aims to define what would be the optimal gut microbiota composition in order to maintain these optimal microbiota immune and metabolic functions.” | |
| contribution — evidence | — “Richness and diversity of gut microbiota shaped in early life characterize a healthy gut microbiota composition. However, this optimal healthy gut microbiota composition is different for each individual.” | |
| transfer | from ecology: 'superorganism', an ecological and evolutionary term for a colony treated as one individual, applied to a human plus their resident microbes — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions” | transfers[0] |
| mechanism | the core native microbiota are set in the first 4-36 months by gestational age, mode of delivery, milk feeding, weaning, lifestyle and diet, and are relatively stable from age 2-3 — “Core native microbiota are shaped in early life (4–36 months) by gut maturation developing from enterotype, birth gestational age, type of delivery, methods of milk feeding, weaning period, lifestyle, and dietary and cultural habits. After a child reaches 2–3 years old, a relative stability in gut microbiota composition has been demonstrated.” | mechanisms[0] |
| mechanism | richness and diversity are what let the ecosystem withstand external threats - unbalanced diet, stress, antibiotics, disease — “Throughout life, the richer and more diverse the microbiota, the better they will withstand external threats. Indeed, gut microbiota represent a changing ecosystem that is severely tested by many factors such as unbalanced diet, stress, antibiotic use, or diseases.” | mechanisms[1] |
| critiques | the search for a single optimal gut microbiota composition, on the ground that the optimum differs for every individual — “These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual.” | claim_relations[0] |
| extends | the dysbiosis literature, by proposing dysbiosis as a BIOMARKER of disorders while stating that the role of gut microbiota is still poorly understood — “Although the role of gut microbiota is still poorly understood, the close association between gut microbiota dysbiosis and intestinal and extra-intestinal disorders has been demonstrated. This is the reason why dysbiosis can be considered as a biomarker of such disorders and that the study of gut microbiota balances shall be one of the priorities for future therapies to prevent and treat diseases.” | claim_relations[1] |
| sense | healthy gut microbiota composition - AS USED HERE: characterised by richness and diversity shaped in early life, and NOT a single composition, because the optimum is different for each individual — “Richness and diversity of gut microbiota shaped in early life characterize a healthy gut microbiota composition. However, this optimal healthy gut microbiota composition is different for each individual.” | senses[0] |
| sense | enterotype - a functional harmonious association of bacterial species, not a systematic addition of them, and EXPLICITLY NOT a clear-cut identity in the way a blood group is — “These three enterotypes are not only enumerations of bacteria; they are also specifically regrouped by functions. Indeed, an enterotype is a functional harmonious association of several bacteria species rather than a systematic addition of bacteria species.” | senses[1] |
| sense | native core microbiota - the profile of a full-term, vaginally delivered, breastfed infant whose mother's milk microbiota is balanced; `healthy` is defined here by PROVENANCE rather than by composition — “These studies have shown that native core microbiota are shaped during early life: the profile of intestinal microbiota in the full-term, vaginally delivered, and breastfed infant with healthy and balanced mother’s milk microbiota is considered healthy.” | senses[2] |
| sense | Microbiome versus microbiota - the review uses microbiome for the gene and metabolite capacity and microbiota for the organisms and their composition — “The human gastrointestinal (GI) tract contains an abundant and diverse microbial community that gathers more than 100 trillion microorganisms [1]. The density of bacterial cells in the colon has been estimated at 1011 to 1012 per milliliter which makes the colon one of the most densely populated microbial habitats known on earth [2]. The gut microbiome encodes over 3 million genes producing thousands of metabolites, whereas the human genome consists of approximately 23,000 genes [3]. For years, scientists have been interested in gut microbiota, but one of the major difficulties in the relevant research has been the ability to culture these microorganisms [4]. During the last years, new technologies have allowed researchers to phylogenetically identify and/or quantify the components of the gut microbiota by analyzing nucleic acids (DNA and RNA) directly extracted from stools. The majority of these techniques are based on the extraction of DNA and the amplification of the 16S ribosomal RNA gene (rRNA) [5, 6]. 16S rRNA sequencing has become the most useful technique to highlight diversity and abundance of the microbiome. The 16S rRNA gene sequences can be exploited with polymerase chain reaction (PCR) and metagenomics sequencing to characterize the microbial strains” | senses[3] |
| sense | Superorganism - the host and resident microorganisms form a symbiotic functional unit while individual species composition remains personal — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions [1]. Gut bacteria are key regulators of digestion along the gastrointestinal tract; commensal bacteria play an important role in the extraction, synthesis, and absorption of many nutrients and metabolites, including bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs). Gut microbiota have a crucial immune function against pathogenic bacteria colonization inhibiting their growth, consuming available nutrients and/or producing bacteriocins. Gut microbiota also prevent bacteria invasion by maintaining the intestinal epithelium integrity [10]. Microorganisms prevent pathogenic colonization by many competition processes: nutrient metabolism, pH modification, antimicrobial peptide secretions, and effects on cell signaling pathways. Moreover, recent studies have identified a critical role for commensal bacteria and their products in regulating the development, homeostasis, and function of innate and adaptive immune cells [11]. It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life” | senses[4] |
| sense | Anatomical gradient - microbial quantity increases toward the large intestine as aerobes give way to strict anaerobes — “Gut microbiota vary according to the intestine anatomical regions, which vary in terms of physiology, pH and O2 tension, digesta flow rates (rapid in the mouth to the caecum, slower afterward), substrate availability, and host secretions [14]. The small intestine provides a more challenging environment for microbial colonizers given the fairly short transit times (3–5 h) and the high bile concentrations. The large intestine, which is characterized by slow flow rates and neutral to mildly acidic pH, harbors by far the largest microbial community (dominated by obligate anaerobic bacteria) [14]. We can observe a microbiota quantitative increasing gradient and a microbiota qualitative decreasing gradient with a progressive aerobic bacteria decrease for the benefit of strictly anaerobic bacteria” | senses[5] |
| sense | Early-life provenance - gestational age, delivery route, milk exposure, and weaning shape a native core before adult stability — “Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions” | senses[6] |
| sense | Antibiotic resilience - community recovery is substantial but repeated exposure can leave memory and a persistent alternative regime — “A cultivation-independent survey of gut microbiota composition of three persons before, during, and after two exposures to the same antibiotic (ciprofloxacin) [48] has been conducted. This study revealed a considerable resilience to antibiotic administration but also suggested that, in some cases, the system retains a memory of past disturbance and that, in all cases, repeated disturbance leads to a persistent regime shift [48]. The impact of antibiotic disturbance on the resilience of microbiota during future antibiotic treatments can thus also vary considerably across individuals” | senses[7] |
| sense | Enterotype function - clusters are organized by shared metabolic functions and substrate use, not merely enumerated bacterial membership — “Gut microbiota of each individual are specifically characterized by clusters of bacteria named enterotypes [13]. Three enterotypes are characterized by three dominant bacteria clusters ( Table 2): Bacteroides (enterotype I), Prevotella (enterotype II), or Ruminococcus (enterotype III). Each enterotype harbors different bacteria genera ( Table 1). These three enterotypes are not only enumerations of bacteria; they are also specifically regrouped by functions. Indeed, an enterotype is a functional harmonious association of several bacteria species rather than a systematic addition of bacteria species. Every enterotype is not a clear-cut identity such as blood groups; however, enterotypes characterize individuals, remain stable from adulthood, and can be restored if they are modified. Each enterotype with its distinctive clusters of bacteria and respective functional characteristics defines a distinctive way of generating energy from fermentable substrates available in the colon. Indeed, bacteria clusters of enterotype I derive energy primarily from carbohydrates using principally glycolysis and pentose phosphate pathways, whereas bacteria clusters of enterotypes II and III are able to degrade mucin glycoproteins of the gut mucosal layer. Enterotypes seem to be principally defined according to dietary habits. Understanding the origins and functions of enterotypes may improve the knowledge of the relationships between gut microbiota and human health” | senses[8] |
| sense | Diet-response timescale - changing to an animal-based diet alters taxa and fermentation activity within about one day — “While the microbiome of a healthy individual is relatively stable, gut microbial dynamics can certainly be influenced by lifestyle and dietary cultural choices [56]. A study of European children (fed with the Western diet) and Burkina Faso children (assuming a diet rich in millet/sorghum + local vegetables containing very few lipids and animal proteins) [57] revealed that African children’s microbiota have a remarkable abundance of Prevotella and Xylanibacter. Furthermore, Shigella and Escherichia are widely under-represented. Another study [58] compared Hadza hunter-gatherers and Italian gut microbiota. At the phylum level, Hadza gut microbiota are largely enriched in Proteobacteria and Spirochaetes, which are extremely rare in the Italian gut microbiota, whereas Actinobacteria, an important subdominant component of the Italian gut microbiota, are almost absent. At the genus level, Hadza gut microbiota are comparatively enriched in Prevotella, Eubacterium, Oscillibacter, Butyricicoccus, Sporobacter, Succinivibrio, and Treponema and correspondingly depleted in Bifidobacterium, Bacteroides, Blautia, Dorea, unclassified Lachnospiraceae, Roseburia, Faecalibacterium, Ruminococcus, and unclassified Erysipelotrichaceae. These two studies showed that African gut microbiota have clearly an enterotype Prevotella (enterotype II); the African diet rich in millet/sorghum + local vegetables containing very few lipids and animal proteins allows a mucine degradation in synergy with Desulfovibrionaceae. European gut microbiota (Western diet) have principally an enterotype Bacteroides (enterotype I): the European diet rich in lipids and animal proteins allows energy production from carbohydrates and proteins through fermentation [13]. David et al. [59] compared plant-based diet microbiome (high fibers and low fats and proteins) with animal-based diet microbiome (low fibers and high fats and proteins) and respective changes in microbiome on either diet and demonstrated that a shift toward an animal-based diet increases the abundance of bile-tolerant microorganisms ( Alistipes, Bilophila, and Bacteroides) and decreases the levels of Firmicutes that metabolize dietary plant polysaccharides ( Roseburia, Eubacterium rectale, and Ruminococcus bromii). Moreover, microbial activity trades off between carbohydrate and protein fermentation when the type of diet respectively changes. This change occurred only one day after the diet reached the distal gut microbiota. David et al. [59] showed that diet alters human microbiota rapidly and reproducibly” | senses[9] |
| sense | Dysbiosis causal boundary - compositional alteration may be either cause or consequence, and the review repeatedly distinguishes association from demonstrated causation — “Gut microbiota composition is highly variable. The variation itself is considered as physiological in the context of healthy gut microbiota, according to age, ethnicity, lifestyle, and dietary habits. However, these physiological gut microbiota variations have huge implications in intestinal and extra-intestinal disorders. Indeed, dysbiosis is often defined as an alteration of gut microbiota composition and a cause or a consequence of disorders. It is often difficult to ascertain whether the change is beneficial or detrimental. As for the human conditions, changes represent a challenge for a better adaptation in a new context and may potentiate resilience. However, a chronic external stimulation may be stressful and disruptive for an unstructured ecosystem. We will discuss the correlations between several diseases and alterations of gut microbiota composition” | senses[10] |
| sense | IBD causal boundary - microbial imbalance is likely to contribute to severity, but the cited results do not demonstrate that it causes IBD pathophysiology — “Inflammatory bowel diseases (IBD) gather idiopathic, chronic, and relapsing inflammatory conditions of the gastrointestinal tract including ulcerative colitis (UC) and Crohn’s disease (CRD). The findings of Frank et al. [66] indicated a diminution of Lachnospiraceae and Bacteroidetes microbial populations and an increase in Proteobacteria families in IBD patients compared to control gut microbiota. Gut microbiota variations appear to be different between UC and CRD. Indeed, a decreased abundance of the butyrate-producing bacteria Roseburia hominis and Faecalibacterium prausnitzii has been observed in UC patients relative to controls [67], whereas the opposite has been observed in CRD patients, who are provided with increased Faecalibacterium prausnitzii levels in addition to a reduced overall diversity [68]. In the case of CRD patients, another study [69] demonstrated a decrease in Dialister invisus, an uncharacterized species of Clostridium spp., in Faecalibacterium prausnitzii, and in Bifidobacterium adolescentis and an increase in Ruminococcus gnavus. Sokol et al. [70] confirmed the reduction of F. prausnitzii in CRD patients and also demonstrated that an oral administration of live Faecalibacterium prausnitzii reduced the severity of colitis and tended to correct the dysbiosis. These results suggest that counterbalancing dysbiosis using Faecalibacterium prausnitzii as a probiotic is a promising strategy in CRD treatment [70]. These results do not demonstrate a causal relationship between microbial dysbiosis and IBD pathophysiology, but they rather suggest that gut microbial unbalances are likely to contribute to disease severity” | senses[11] |
| sense | Obesity evidence boundary - animal studies provide most causal evidence while human microbial-composition data are more variable — “Animal studies constitute the majority of causative evidence linking changes in microbial composition to obesity while, in humans, data are more variable. In addition, although the majority of mouse gut species are unique, the mouse and human microbiota are similar at the division level, with Firmicutes and Bacteroidetes dominating [83]. The analysis [83] of gut microbiota of genetically obese ob/ob mice and lean mice all fed the same polysaccharide-rich diet revealed a lower relative abundance (50%) of Bacteroidetes in obese ob/ob mice, whereas the Firmicutes are correspondingly higher. Indeed, higher numbers of Ruminococcaceae and Rikenellaceae have been observed in leptin-resistant obese (leptin-promoting satiety) and diabetic mice (db/db) compared with their lean littermates [84]. In addition, the higher abundance of Ruminococcaceae and Rikenellaceae in mice fed a high-fat diet is not only dependent on the ingested diet but is also closely linked with obesity and type 2 diabetes [85]. Furthermore, the association between Desulfovibrionaceae abundance and obesity and type 2 diabetes has been demonstrated [86, 87]. Other studies [50, 88] confirmed the role of Proteobacteria in obesity by producing pro-inflammatory molecules such as lipopolysaccharides and helping to harvest energy and increase host fat storage [88]. On the contrary, researchers [86, 89] have recently demonstrated that Akkermansia muciniphila, a mucin-degrading bacteria living in the mucus layer [90], decreases in both genetically and diet-induced obese mice. All these studies highlight the finding that obesity is associated with changes in the composition of gut microbiota including lower species diversity and shifts in the abundance of genes involved in metabolism. These gut microbiota variations affect the microbiome which has an increased capacity to harvest energy from the diet and these changes are transmissible [91]. Gut microbiota can be considered as a contributing factor to the pathophysiology of obesity and may have potential therapeutic implications” | senses[12] |
| sense | Gut-brain directionality - the brain influences gastrointestinal and immune functions, while gut dysbiosis is also linked to neuroinflammatory pathology — “The brain and the gut are connected via the gut–brain axis with bidirectional interactions between the central nervous system, the enteric nervous system, and the gastrointestinal tract. These bidirectional interactions enable the brain to influence gastrointestinal functions as well as immune functions” | senses[13] |
| sense | Healthy composition as resilience - no universal species profile is asserted; richness, diversity, balance, and resistance to disturbance are the operative properties — “Each healthy human is provided with unique gut microbiota. Core native microbiota are shaped in early life (4–36 months) by gut maturation developing from enterotype, birth gestational age, type of delivery, methods of milk feeding, weaning period, lifestyle, and dietary and cultural habits. After a child reaches 2–3 years old, a relative stability in gut microbiota composition has been demonstrated. Richness and diversity of gut microbiota shaped in early life characterize a healthy gut microbiota composition. However, this optimal healthy gut microbiota composition is different for each individual. Throughout life, the richer and more diverse the microbiota, the better they will withstand external threats. Indeed, gut microbiota represent a changing ecosystem that is severely tested by many factors such as unbalanced diet, stress, antibiotic use, or diseases. A healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. Indeed, disturbances to the delicate host–microbe relationship may disrupt the development of the immune system, which may in turn result in diseases [113]. Although the role of gut microbiota is still poorly understood, the close association between gut microbiota dysbiosis and intestinal and extra-intestinal disorders has been demonstrated. This is the reason why dysbiosis can be considered as a biomarker of such disorders and that the study of gut microbiota balances shall be one of the priorities for future therapies to prevent and treat diseases” | senses[14] |
| control | microbiota variation is reported WITHIN the same individual as well as BETWEEN individuals, so a between-person difference is not read as a change — held — “These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual.” — rules out inter-individual variation being reported as the effect of an exposure — “It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life.” | controls[0] |
| control | the direction of the microbiota-disease association is left open rather than asserted — absent-declared-unreported — “Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions.” | controls[1] |
| weight | the search for a single optimal gut microbiota composition, on the ground that the optimum differs for every individual — 0.9 — “These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual.” | claim_relations[0] |
| weight | the dysbiosis literature, by proposing dysbiosis as a BIOMARKER of disorders while stating that the role of gut microbiota is still poorly understood — 0.9 — “Although the role of gut microbiota is still poorly understood, the close association between gut microbiota dysbiosis and intestinal and extra-intestinal disorders has been demonstrated. This is the reason why dysbiosis can be considered as a biomarker of such disorders and that the study of gut microbiota balances shall be one of the priorities for future therapies to prevent and treat diseases.” | claim_relations[1] |
| differs in (stated by the tagger, no quotation) | enterotype —distinct-from→ blood groups — whether the category is fixed and exclusive, or stable-but-modifiable | concept_edges[0] |
| relation | enterotype —distinct-from→ blood groups — an enterotype is NOT a clear-cut identity in the way a blood group is - it characterises an individual, is stable from adulthood, and CAN BE RESTORED IF MODIFIED, which a blood group cannot — “Every enterotype is not a clear-cut identity such as blood groups; however, enterotypes characterize individuals, remain stable from adulthood, and can be restored if they are modified.” | concept_edges[0] |
| weight | enterotype —distinct-from→ blood groups — 0.95 — “Every enterotype is not a clear-cut identity such as blood groups; however, enterotypes characterize individuals, remain stable from adulthood, and can be restored if they are modified.” | concept_edges[0] |
| relation | bacteria species —part-of→ gut microbiota — gut microbiota are composed of bacteria species, classified by genus, family, order and phylum - the level at which every composition claim is stated — “Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla.” | concept_edges[1] |
| weight | bacteria species —part-of→ gut microbiota — 0.9 — “Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla.” | concept_edges[1] |
| note | Clostridium —part-of→ Firmicutes phylum — Clostridium is included among genera composing Firmicutes. — “The Firmicutes phylum is composed of more than 200 different genera such as Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus. Clostridium genera represent 95” | concept_edges[2] |
| note | Bacteroides —part-of→ Bacteroidetes — Bacteroidetes is explicitly said to consist of predominant genera including Bacteroides. — “Bacteroidetes consists of predominant genera such as Bacteroides and Prevotella. The Actinobacteria phylum is proportionally less abundant and mainly represented by the Bifidobacterium genus” | concept_edges[3] |
| differs in (stated by the tagger, no quotation) | formula-fed infants —contrasted-with→ breastfed infants — colonization by E. coli, Bacteroides, and C. difficile | concept_edges[4] |
| note | formula-fed infants —contrasted-with→ breastfed infants — The feeding groups are directly compared. — “formula-fed infants are more often colonized with Escherichia coli, Bacteroides, and Clostridium difficile compared with breastfed infants” | concept_edges[4] |
| effect direction | fermentation of galactooligosaccharide (GOS) —causes→ SCFAs — increases — “Bifidobacterium_ spp. are responsible for the fermentation of galactooligosaccharide (GOS), one of the main components of breast milk, to produce SCFAs” | concept_edges[5] |
| note | fermentation of galactooligosaccharide (GOS) —causes→ SCFAs — Bifidobacterial GOS fermentation is stated to produce short-chain fatty acids. — “Bifidobacterium_ spp. are responsible for the fermentation of galactooligosaccharide (GOS), one of the main components of breast milk, to produce SCFAs” | concept_edges[5] |
| effect direction | high-fiber and carbohydrate foods —causes→ Firmicutes — increases — “The introduction of high-fiber and carbohydrate foods (traditional foods) causes an increase in Firmicutes and Prevotella, whereas the introduction of high-fiber and animal protein foods causes an increase in Bacteroidetes” | concept_edges[6] |
| note | high-fiber and carbohydrate foods —causes→ Firmicutes — The paper directly states that introduction of these foods causes an increase in Firmicutes. — “The introduction of high-fiber and carbohydrate foods (traditional foods) causes an increase in Firmicutes and Prevotella, whereas the introduction of high-fiber and animal protein foods causes an increase in Bacteroidetes” | concept_edges[6] |
| effect direction | high-fiber and carbohydrate foods —causes→ Prevotella — increases — “The introduction of high-fiber and carbohydrate foods (traditional foods) causes an increase in Firmicutes and Prevotella, whereas the introduction of high-fiber and animal protein foods causes an increase in Bacteroidetes” | concept_edges[7] |
| note | high-fiber and carbohydrate foods —causes→ Prevotella — The paper directly states that introduction of these foods causes an increase in Prevotella. — “The introduction of high-fiber and carbohydrate foods (traditional foods) causes an increase in Firmicutes and Prevotella, whereas the introduction of high-fiber and animal protein foods causes an increase in Bacteroidetes” | concept_edges[7] |
| effect direction | high-fiber and animal protein foods —causes→ Bacteroidetes — increases — “The introduction of high-fiber and carbohydrate foods (traditional foods) causes an increase in Firmicutes and Prevotella, whereas the introduction of high-fiber and animal protein foods causes an increase in Bacteroidetes” | concept_edges[8] |
| note | high-fiber and animal protein foods —causes→ Bacteroidetes — The alternative weaning diet is directly said to cause an increase in Bacteroidetes. — “The introduction of high-fiber and carbohydrate foods (traditional foods) causes an increase in Firmicutes and Prevotella, whereas the introduction of high-fiber and animal protein foods causes an increase in Bacteroidetes” | concept_edges[8] |
| note | Broad-spectrum antibiotics —causes→ imbalance between Firmicutes and Bacteroidetes — Broad-spectrum antibiotics are stated to lead to the phylum imbalance. — “Broad-spectrum antibiotics lead to an imbalance between Firmicutes and Bacteroidetes. The bacterial diversity decreases and so does the abundance of these bacteria during the treatments” | concept_edges[9] |
| audit | repeated disturbance —causes→ persistent regime shift — Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but attributed: the span reports what a cited study suggested about repeated disturbance. — “This study revealed a considerable resilience to antibiotic administration but also suggested that, in some cases, the system retains a memory of past disturbance and that, in all cases, repeated disturbance leads to a persistent regime shift [48]. The impact of antibiotic disturbance on the resilience of microbiota during future antibiotic treatments” | concept_edges[10] |
| note | repeated disturbance —causes→ persistent regime shift — The three-person antibiotic study suggests that repeated disturbance leads to a persistent shift. — “This study revealed a considerable resilience to antibiotic administration but also suggested that, in some cases, the system retains a memory of past disturbance and that, in all cases, repeated disturbance leads to a persistent regime shift [48]. The impact of antibiotic disturbance on the resilience of microbiota during future antibiotic treatments” | concept_edges[10] |
| relation | repeated disturbance —causes→ persistent regime shift — repeated disturbance leads to a persistent regime shift \ [48\]. The impact of antibiotic disturbance on the resilience of microbiota during future antibiotic treatments — “This study revealed a considerable resilience to antibiotic administration but also suggested that, in some cases, the system retains a memory of past disturbance and that, in all cases, repeated disturbance leads to a persistent regime shift [48]. The impact of antibiotic disturbance on the resilience of microbiota during future antibiotic treatments” | concept_edges[10] |
| weight | repeated disturbance —causes→ persistent regime shift — 0.9 — “This study revealed a considerable resilience to antibiotic administration but also suggested that, in some cases, the system retains a memory of past disturbance and that, in all cases, repeated disturbance leads to a persistent regime shift [48]. The impact of antibiotic disturbance on the resilience of microbiota during future antibiotic treatments” | concept_edges[10] |
| effect direction | Daily exercise —causes→ gut microbial diversity — increases — “Daily exercise increases gut microbial diversity ( Table 2) with a Firmicutes enrichment microbiota: Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae by producing more SCFAs which may increase the expression of tight junction proteins in colon epithelia to heighten the resistance of the intestinal barrier, reduce mucosal permeability, and inhibit inflammatory cytokines” | concept_edges[11] |
| note | Daily exercise —causes→ gut microbial diversity — The reviewed evidence directly states that daily exercise increases diversity. — “Daily exercise increases gut microbial diversity ( Table 2) with a Firmicutes enrichment microbiota: Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae by producing more SCFAs which may increase the expression of tight junction proteins in colon epithelia to heighten the resistance of the intestinal barrier, reduce mucosal permeability, and inhibit inflammatory cytokines” | concept_edges[11] |
| audit | SCFAs —causes→ expression of tight junction proteins — Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span says SCFAs MAY increase the expression of tight junction proteins; hedged. — “Daily exercise increases gut microbial diversity ( Table 2) with a Firmicutes enrichment microbiota: Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae by producing more SCFAs which may increase the expression of tight junction proteins in colon epithelia to heighten the resistance of the intestinal barrier, reduce mucosal permeability, and inhibit inflammatory cytokines” | concept_edges[12] |
| effect direction | SCFAs —causes→ expression of tight junction proteins — increases — “Daily exercise increases gut microbial diversity ( Table 2) with a Firmicutes enrichment microbiota: Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae by producing more SCFAs which may increase the expression of tight junction proteins in colon epithelia to heighten the resistance of the intestinal barrier, reduce mucosal permeability, and inhibit inflammatory cytokines” | concept_edges[12] |
| note | SCFAs —causes→ expression of tight junction proteins — The paper says exercise-associated SCFAs may increase tight-junction expression. — “Daily exercise increases gut microbial diversity ( Table 2) with a Firmicutes enrichment microbiota: Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae by producing more SCFAs which may increase the expression of tight junction proteins in colon epithelia to heighten the resistance of the intestinal barrier, reduce mucosal permeability, and inhibit inflammatory cytokines” | concept_edges[12] |
| weight | SCFAs —causes→ expression of tight junction proteins — 0.7 — “Daily exercise increases gut microbial diversity ( Table 2) with a Firmicutes enrichment microbiota: Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae by producing more SCFAs which may increase the expression of tight junction proteins in colon epithelia to heighten the resistance of the intestinal barrier, reduce mucosal permeability, and inhibit inflammatory cytokines” | concept_edges[12] |
| note | dysbiosis —operationalised-as→ alteration of gut microbiota composition — The weight reflects the qualifier 'often defined'. — “dysbiosis is often defined as an alteration of gut microbiota composition and a cause or a consequence of disorders” | concept_edges[13] |
| weight | dysbiosis —operationalised-as→ alteration of gut microbiota composition — 0.9 — “dysbiosis is often defined as an alteration of gut microbiota composition and a cause or a consequence of disorders” | concept_edges[13] |
| note | ulcerative colitis (UC) —part-of→ inflammatory bowel diseases (IBD) — IBD is explicitly said to include ulcerative colitis. — “Inflammatory bowel diseases (IBD) gather idiopathic, chronic, and relapsing inflammatory conditions of the gastrointestinal tract including ulcerative colitis (UC) and Crohn’s disease (CRD)” | concept_edges[14] |
| note | Crohn’s disease (CRD) —part-of→ inflammatory bowel diseases (IBD) — IBD is explicitly said to include Crohn's disease. — “Inflammatory bowel diseases (IBD) gather idiopathic, chronic, and relapsing inflammatory conditions of the gastrointestinal tract including ulcerative colitis (UC) and Crohn’s disease (CRD)” | concept_edges[15] |
| audit | oral administration —causes→ severity of colitis — Audit 2026-09-28: DOUBTFUL - read against its span and kept, but oral F. prausnitzii REDUCED colitis severity; the edge lacks its direction (reduces). — “oral administration of live Faecalibacterium prausnitzii reduced the severity of colitis and tended to correct the dysbiosis” | concept_edges[16] |
| note | oral administration —causes→ severity of colitis — The cited intervention reduced colitis severity. — “oral administration of live Faecalibacterium prausnitzii reduced the severity of colitis and tended to correct the dysbiosis” | concept_edges[16] |
| note | interplay between gluten, genetic factors, and environmental factors —causes→ Celiac disease — The paper explicitly states that celiac disease is caused by this interplay. — “Celiac disease is caused by the interplay between gluten, genetic factors, and environmental factors such as gut microbiota” | concept_edges[17] |
| audit | neuroinflammation —causes→ PD pathology — Audit 2026-09-28: DOUBTFUL - read against its span and kept, but dysbiosis 'MAY be' the mechanism of neuroinflammation leading to PD; causes is hedged. — “gut microbiota dysbiosis may be the mechanism of neuroinflammation that leads to PD pathology” | concept_edges[18] |
| note | neuroinflammation —causes→ PD pathology — The proposed mechanism is hedged with 'may' but explicitly says neuroinflammation leads to pathology. — “gut microbiota dysbiosis may be the mechanism of neuroinflammation that leads to PD pathology” | concept_edges[18] |
| weight | neuroinflammation —causes→ PD pathology — 0.7 — “gut microbiota dysbiosis may be the mechanism of neuroinflammation that leads to PD pathology” | concept_edges[18] |
| note | exposure to stress —causes→ substantial changes in gut microbiota composition — The social-disruption model states that stress exposure results in the changes. — “exposure to stress results in substantial changes in gut microbiota composition: a decrease in Bacteroides spp. abundance and an increase in Clostridium spp. abundance have been observed in stress-induced mice relative to controls” | concept_edges[19] |
| note | disturbances to the delicate host–microbe relationship —causes→ diseases — The conclusion uses two 'may' hedges for disruption of immune development and disease. — “disturbances to the delicate host–microbe relationship may disrupt the development of the immune system, which may in turn result in diseases” | concept_edges[20] |
| weight | disturbances to the delicate host–microbe relationship —causes→ diseases — 0.7 — “disturbances to the delicate host–microbe relationship may disrupt the development of the immune system, which may in turn result in diseases” | concept_edges[20] |
| outcome | control — held — “It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life.” — “These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual.” | controls[0] |
| outcome (stated by the tagger, no quotation) | control — absent-declared-unreported | controls[1] |
| weight | human milk oligosaccharides (HMOs) → necrotizing enterocolitis (NEC) — 0.6 — “Human milk composition depends on genetic factors and the mother’s secretor and Lewis blood groups defining four phenotypes characterized by different levels of oligosaccharide amounts [18]. Higher levels of Proteobacteria and lower levels of Firmicutes are noted in premature infants of non-secretor mothers [19]. A recent study by Praticò et al. [20] characterizing human breast milk composition demonstrated that human milk oligosaccharides (HMOs) related to different mother phenotypes modulate gut microbiota composition in infants. Specifically, HMOs associated with secretor mothers may have a protective prebiotic effect by decreasing pathogens associated with sepsis and necrotizing enterocolitis (NEC) [19]. This indicates that HMOs may influence the intestinal microbiota and prevent gut dysfunction and NEC in preterm infants” | unhoused_relations[2] |
| weight | dysbiosis → biomarker — 0.8 — “Each healthy human is provided with unique gut microbiota. Core native microbiota are shaped in early life (4–36 months) by gut maturation developing from enterotype, birth gestational age, type of delivery, methods of milk feeding, weaning period, lifestyle, and dietary and cultural habits. After a child reaches 2–3 years old, a relative stability in gut microbiota composition has been demonstrated. Richness and diversity of gut microbiota shaped in early life characterize a healthy gut microbiota composition. However, this optimal healthy gut microbiota composition is different for each individual. Throughout life, the richer and more diverse the microbiota, the better they will withstand external threats. Indeed, gut microbiota represent a changing ecosystem that is severely tested by many factors such as unbalanced diet, stress, antibiotic use, or diseases. A healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. Indeed, disturbances to the delicate host–microbe relationship may disrupt the development of the immune system, which may in turn result in diseases [113]. Although the role of gut microbiota is still poorly understood, the close association between gut microbiota dysbiosis and intestinal and extra-intestinal disorders has been demonstrated. This is the reason why dysbiosis can be considered as a biomarker of such disorders and that the study of gut microbiota balances shall be one of the priorities for future therapies to prevent and treat diseases” | unhoused_relations[8] |
| weight | gut bacterial communities → therapeutic interventions — 0.7 — “The bidirectional interactions of gut–brain mean that the brain can also alter gut microbiota composition [110]. A model of social disruption among adult mice [111] demonstrated that exposure to stress results in substantial changes in gut microbiota composition: a decrease in Bacteroides spp. abundance and an increase in Clostridium spp. abundance have been observed in stress-induced mice relative to controls. The mechanisms by which stress influences gut microbiota composition are unclear but include microbial habitat alterations following stress-induced changes in intestinal mobility and mucin secretion [110, 112]. Other studies [62] revealed that chronic psychological stress is reflected in the microbiota composition. Indeed, depression due to chronic stressful life events is associated with an increase in Enterobacteriaceae, whereas psychological stress is associated with a reduction in Lactobacilli spp. and an increase in Escherichia coli and Pseudomonas spp. Gut microbiota variations are closely associated with the onset of these neurological disorders, and the gut bacterial communities may be a target for therapeutic interventions” | unhoused_relations[9] |
| no type for this | 16S rRNA sequencing → diversity and abundance of the microbiome — 16S sequencing is used to highlight microbiome diversity and abundance; measures-or-characterizes is absent from the eight governed types. — “The human gastrointestinal (GI) tract contains an abundant and diverse microbial community that gathers more than 100 trillion microorganisms [1]. The density of bacterial cells in the colon has been estimated at 1011 to 1012 per milliliter which makes the colon one of the most densely populated microbial habitats known on earth [2]. The gut microbiome encodes over 3 million genes producing thousands of metabolites, whereas the human genome consists of approximately 23,000 genes [3]. For years, scientists have been interested in gut microbiota, but one of the major difficulties in the relevant research has been the ability to culture these microorganisms [4]. During the last years, new technologies have allowed researchers to phylogenetically identify and/or quantify the components of the gut microbiota by analyzing nucleic acids (DNA and RNA) directly extracted from stools. The majority of these techniques are based on the extraction of DNA and the amplification of the 16S ribosomal RNA gene (rRNA) [5, 6]. 16S rRNA sequencing has become the most useful technique to highlight diversity and abundance of the microbiome. The 16S rRNA gene sequences can be exploited with polymerase chain reaction (PCR) and metagenomics sequencing to characterize the microbial strains” | unhoused_relations[0] |
| no type for this | gut microbiota → metabolic and immune functions — Gut microbiota perform metabolic and immune functions; performs-function-for is absent from the governed types. — “Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions” | unhoused_relations[1] |
| no type for this | human milk oligosaccharides (HMOs) → necrotizing enterocolitis (NEC) — HMOs may have a protective prebiotic effect that helps prevent NEC; protective-against is absent from the eight types and the claim is explicitly hedged. — “Human milk composition depends on genetic factors and the mother’s secretor and Lewis blood groups defining four phenotypes characterized by different levels of oligosaccharide amounts [18]. Higher levels of Proteobacteria and lower levels of Firmicutes are noted in premature infants of non-secretor mothers [19]. A recent study by Praticò et al. [20] characterizing human breast milk composition demonstrated that human milk oligosaccharides (HMOs) related to different mother phenotypes modulate gut microbiota composition in infants. Specifically, HMOs associated with secretor mothers may have a protective prebiotic effect by decreasing pathogens associated with sepsis and necrotizing enterocolitis (NEC) [19]. This indicates that HMOs may influence the intestinal microbiota and prevent gut dysfunction and NEC in preterm infants” | unhoused_relations[2] |
| no type for this | Lactoferrin (LF) → beneficial bacteria — Lactoferrin favors infant-gut colonization by beneficial bacteria; favors-colonization is absent from the eight governed types. — “Lactoferrin (LF) is another well-known component of human milk favoring gut infant colonization with beneficial bacteria and consequently representing a crucial role played in preterm infants’ microbiota [22]. Indeed, correlations between LF and beneficial microbiota in breast milk and infant’s feces have been demonstrated [22]. High levels of fecal LF, particularly in preterm infants, may represent an important factor in the initiation, development, and/or composition of the neonatal gut microbiota contributing to the immunologic maturation and well-being of the newborn, especially in preterm infants [22]. Therefore, a mother’s own milk helps to shape developing core gut microbiota that can improve growth and neurodevelopment and decrease the risk of NEC and late-onset sepsis [19, 21]. It is for all these reasons that human milk should be the primary enteral diet of premature infants” | unhoused_relations[3] |
| no type for this | enterotype → distinctive way of generating energy from fermentable substrates — Each enterotype defines a distinctive energy-generation strategy; defines-functional-strategy is absent from the governed relation types. — “Gut microbiota of each individual are specifically characterized by clusters of bacteria named enterotypes [13]. Three enterotypes are characterized by three dominant bacteria clusters ( Table 2): Bacteroides (enterotype I), Prevotella (enterotype II), or Ruminococcus (enterotype III). Each enterotype harbors different bacteria genera ( Table 1). These three enterotypes are not only enumerations of bacteria; they are also specifically regrouped by functions. Indeed, an enterotype is a functional harmonious association of several bacteria species rather than a systematic addition of bacteria species. Every enterotype is not a clear-cut identity such as blood groups; however, enterotypes characterize individuals, remain stable from adulthood, and can be restored if they are modified. Each enterotype with its distinctive clusters of bacteria and respective functional characteristics defines a distinctive way of generating energy from fermentable substrates available in the colon. Indeed, bacteria clusters of enterotype I derive energy primarily from carbohydrates using principally glycolysis and pentose phosphate pathways, whereas bacteria clusters of enterotypes II and III are able to degrade mucin glycoproteins of the gut mucosal layer. Enterotypes seem to be principally defined according to dietary habits. Understanding the origins and functions of enterotypes may improve the knowledge of the relationships between gut microbiota and human health” | unhoused_relations[4] |
| no type for this | BMI levels → gut microbiota dysbiosis — BMI levels are assigned predictive value for dysbiosis; predicts is absent from the eight governed types. — “have examined the impact of childhood BMI on gut microbiota composition and demonstrated that children with overweight or normal BMI are provided with a higher microbial diversity than underweight children. Gut microbiota diversity descends stepwise based on BMI class [50, 52]. Bervoets et al. [53] demonstrated that the microbiota of obese children are provided with an elevated Firmicutes-to-Bacteroidetes ratio compared to the microbiota of lean children [53]. Furthermore, low relative proportions of Bifidobacterium vulgatus and high concentrations of Lactobacillus spp. are observed in the obese microbiota [53]. Riva et al. [54] confirmed that obesity is associated with elevated levels of Firmicutes such as Ruminococcaceae and depleted levels of Bacteroidetes such as Bacteroidaceae and Bacteroides. SCFAs are higher in obese children suggesting elevated substrate utilization. These findings suggest that the dysbiosis of gut microbiota may contribute to the pathophysiology of obesity and the increased ratio of Firmicutes to Bacteroidetes is associated with the increased production of SCFAs and energy harvest from colonic fermentation [54]. The underweight BMI level also revealed profound gut microbiota variations. Borgo et al. [55] performed a comprehensive data analysis comparing gut microbiota and anthropometric traits of 15 anorexia nervosa (AN) women and healthy controls. Results showed that AN intestinal microbiota showed a significant increase in Enterobacteriaceae and Methanobrevibacter smithii compared with healthy controls [55]. On the contrary, the genera Roseburia, Ruminococcus, and Clostridium were depleted in line with the observed reduction in AN of the total SCFAs [55]. BMI levels represent a valid predictive value for gut microbiota dysbiosis. Studies have demonstrated that gut microbiota variations are correlated with increased or depleted production of SCFAs that may respectively contribute to the pathophysiology of obesity or AN. Interventions such as prebiotics and probiotics may be possible solutions to manage both pediatric obesity” | unhoused_relations[5] |
| no type for this | dysbiosis → intestinal and extra-intestinal disorders — The review reports a close association between dysbiosis and both intestinal and extra-intestinal disorders while withholding a single causal direction; associated-with is absent. — “Each healthy human is provided with unique gut microbiota. Core native microbiota are shaped in early life (4–36 months) by gut maturation developing from enterotype, birth gestational age, type of delivery, methods of milk feeding, weaning period, lifestyle, and dietary and cultural habits. After a child reaches 2–3 years old, a relative stability in gut microbiota composition has been demonstrated. Richness and diversity of gut microbiota shaped in early life characterize a healthy gut microbiota composition. However, this optimal healthy gut microbiota composition is different for each individual. Throughout life, the richer and more diverse the microbiota, the better they will withstand external threats. Indeed, gut microbiota represent a changing ecosystem that is severely tested by many factors such as unbalanced diet, stress, antibiotic use, or diseases. A healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. Indeed, disturbances to the delicate host–microbe relationship may disrupt the development of the immune system, which may in turn result in diseases [113]. Although the role of gut microbiota is still poorly understood, the close association between gut microbiota dysbiosis and intestinal and extra-intestinal disorders has been demonstrated. This is the reason why dysbiosis can be considered as a biomarker of such disorders and that the study of gut microbiota balances shall be one of the priorities for future therapies to prevent and treat diseases” | unhoused_relations[6] |
| no type for this | brain → gut — The brain and gut are connected through a bidirectional gut-brain axis; connected-via is absent from the eight types. — “The brain and the gut are connected via the gut–brain axis with bidirectional interactions between the central nervous system, the enteric nervous system, and the gastrointestinal tract. These bidirectional interactions enable the brain to influence gastrointestinal functions as well as immune functions” | unhoused_relations[7] |
| no type for this | dysbiosis → biomarker — Dysbiosis is proposed as a biomarker of intestinal and extra-intestinal disorders; biomarker-of is absent from the eight governed types. — “Each healthy human is provided with unique gut microbiota. Core native microbiota are shaped in early life (4–36 months) by gut maturation developing from enterotype, birth gestational age, type of delivery, methods of milk feeding, weaning period, lifestyle, and dietary and cultural habits. After a child reaches 2–3 years old, a relative stability in gut microbiota composition has been demonstrated. Richness and diversity of gut microbiota shaped in early life characterize a healthy gut microbiota composition. However, this optimal healthy gut microbiota composition is different for each individual. Throughout life, the richer and more diverse the microbiota, the better they will withstand external threats. Indeed, gut microbiota represent a changing ecosystem that is severely tested by many factors such as unbalanced diet, stress, antibiotic use, or diseases. A healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. Indeed, disturbances to the delicate host–microbe relationship may disrupt the development of the immune system, which may in turn result in diseases [113]. Although the role of gut microbiota is still poorly understood, the close association between gut microbiota dysbiosis and intestinal and extra-intestinal disorders has been demonstrated. This is the reason why dysbiosis can be considered as a biomarker of such disorders and that the study of gut microbiota balances shall be one of the priorities for future therapies to prevent and treat diseases” | unhoused_relations[8] |
| no type for this | gut bacterial communities → therapeutic interventions — Gut bacterial communities are proposed as targets for therapeutic intervention; target-of-intervention is absent from the governed types. — “The bidirectional interactions of gut–brain mean that the brain can also alter gut microbiota composition [110]. A model of social disruption among adult mice [111] demonstrated that exposure to stress results in substantial changes in gut microbiota composition: a decrease in Bacteroides spp. abundance and an increase in Clostridium spp. abundance have been observed in stress-induced mice relative to controls. The mechanisms by which stress influences gut microbiota composition are unclear but include microbial habitat alterations following stress-induced changes in intestinal mobility and mucin secretion [110, 112]. Other studies [62] revealed that chronic psychological stress is reflected in the microbiota composition. Indeed, depression due to chronic stressful life events is associated with an increase in Enterobacteriaceae, whereas psychological stress is associated with a reduction in Lactobacilli spp. and an increase in Escherichia coli and Pseudomonas spp. Gut microbiota variations are closely associated with the onset of these neurological disorders, and the gut bacterial communities may be a target for therapeutic interventions” | unhoused_relations[9] |
| limitation | THE PAPER'S TITLE ASKS FOR A NORM AND ITS ANSWER IS THAT THERE IS NONE: there is no unique optimal gut microbiota composition, because it differs for each individual - while `dysbiosis`, defined by departure from that composition, continues to be used — “These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual.” | limitations[0] |
| limitation | whether the microbiota balances are the CAUSE or the CONSEQUENCE of disease is explicitly unresolved, and the therapeutic proposal rests on resolving it — “Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions.” | limitations[1] |
| limitation | the role of gut microbiota is stated by the authors to be still poorly understood, in the same sentence that proposes dysbiosis as a biomarker — “Although the role of gut microbiota is still poorly understood, the close association between gut microbiota dysbiosis and intestinal and extra-intestinal disorders has been demonstrated. This is the reason why dysbiosis can be considered as a biomarker of such disorders and that the study of gut microbiota balances shall be one of the priorities for future therapies to prevent and treat diseases.” | limitations[2] |
| limitation | the field's foundational difficulty was that these organisms could not be cultured, so the composition literature rests on 16S rRNA sequencing of DNA from stools rather than on the organisms themselves — “For years, scientists have been interested in gut microbiota, but one of the major difficulties in the relevant research has been the ability to culture these microorganisms” | limitations[3] |
| limitation | resilience to antibiotic disturbance varies considerably across individuals, so a population-level statement about recovery does not transfer to a person — “The impact of antibiotic disturbance on the resilience of microbiota during future antibiotic treatments can thus also vary considerably across individuals” | limitations[4] |
Content tags
content-observations:
finding · quantity · variable · definition · key-term — grounded in the full text| finding | — “These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual.” | content_tags.findings[0] |
| finding | — “It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life.” | content_tags.findings[1] |
| finding | — “Throughout life, the richer and more diverse the microbiota, the better they will withstand external threats. Indeed, gut microbiota represent a changing ecosystem that is severely tested by many factors such as unbalanced diet, stress, antibiotic use, or diseases.” | content_tags.findings[2] |
| finding | — “Every enterotype is not a clear-cut identity such as blood groups; however, enterotypes characterize individuals, remain stable from adulthood, and can be restored if they are modified.” | content_tags.findings[3] |
| finding | — “Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions.” | content_tags.findings[4] |
| quantity | microorganisms in the human gastrointestinal tract — “The human gastrointestinal (GI) tract contains an abundant and diverse microbial community that gathers more than 100 trillion microorganisms” | content_tags.quantities[0] |
| quantity | genes encoded by the gut microbiome, against approximately 23,000 in the human genome — “The gut microbiome encodes over 3 million genes producing thousands of metabolites, whereas the human genome consists of approximately 23,000 genes” | content_tags.quantities[1] |
| quantity | species, from only a few phyla, represented in the gut — “Only a few phyla are represented, accounting for more than 160 species” | content_tags.quantities[2] |
| quantity | months - the window in which the core native microbiota are shaped, with relative stability from age 2-3 — “Core native microbiota are shaped in early life (4–36 months) by gut maturation developing from enterotype, birth gestational age, type of delivery, methods of milk feeding, weaning period, lifestyle, and dietary and cultural habits. After a child reaches 2–3 years old, a relative stability in gut microbiota composition has been demonstrated.” | content_tags.quantities[3] |
| variable | diversity — “Throughout life, the richer and more diverse the microbiota, the better they will withstand external threats. Indeed, gut microbiota represent a changing ecosystem that is severely tested by many factors such as unbalanced diet, stress, antibiotic use, or diseases.” | content_tags.variables[0] |
| variable | enterotype — “Gut microbiota of each individual are specifically characterized by clusters of bacteria named enterotypes [13]. Three enterotypes are characterized by three dominant bacteria clusters ( Table 2): Bacteroides (enterotype I), Prevotella (enterotype II), or Ruminococcus (enterotype III).” | content_tags.variables[1] |
| variable | type of delivery — “Core native microbiota are shaped in early life (4–36 months) by gut maturation developing from enterotype, birth gestational age, type of delivery, methods of milk feeding, weaning period, lifestyle, and dietary and cultural habits. After a child reaches 2–3 years old, a relative stability in gut microbiota composition has been demonstrated.” | content_tags.variables[2] |
| definition | enterotype — “These three enterotypes are not only enumerations of bacteria; they are also specifically regrouped by functions. Indeed, an enterotype is a functional harmonious association of several bacteria species rather than a systematic addition of bacteria species.” | content_tags.definitions[0] |
| definition | superorganism — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions” | content_tags.definitions[1] |
| definition | native core microbiota — “These studies have shown that native core microbiota are shaped during early life: the profile of intestinal microbiota in the full-term, vaginally delivered, and breastfed infant with healthy and balanced mother’s milk microbiota is considered healthy.” | content_tags.definitions[2] |
Concepts
terms this paper carries, each with the sentence it was cut from — the layer that joins one paper to another. Terms with no quote yet are on CONCEPTS.html.
| concept | gut microbiota — not defined in this paper's own words; the microbial community of the GI tract, over 100 trillion organisms, treated as one object with a composition that can be healthy or not — “The human gastrointestinal (GI) tract contains an abundant and diverse microbial community that gathers more than 100 trillion microorganisms” | concepts[0] |
| concept | enterotype — not defined in this paper's own words; one of three clusters named for a dominant genus - Bacteroides, Prevotella, Ruminococcus - grouped by function rather than by membership — “Gut microbiota of each individual are specifically characterized by clusters of bacteria named enterotypes [13]. Three enterotypes are characterized by three dominant bacteria clusters ( Table 2): Bacteroides (enterotype I), Prevotella (enterotype II), or Ruminococcus (enterotype III).” | concepts[1] |
| concept | blood groups — not defined in this paper's own words; the clear-cut identity an enterotype is explicitly NOT - the paper names the category it is being distinguished from, which is what a controlled vocabulary needs and rarely gets — “Every enterotype is not a clear-cut identity such as blood groups; however, enterotypes characterize individuals, remain stable from adulthood, and can be restored if they are modified.” | concepts[2] |
| concept | bacteria species — not defined in this paper's own words; the taxonomic unit the composition is counted in - classified by genus, family, order and phylum, and the level at which 'composition' is stated — “Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla.” | concepts[3] |
| concept | dysbiosis — not defined in this paper's own words; departure from a healthy composition, associated with intestinal AND extra-intestinal disease, and proposed as a biomarker while its direction of causation is unsettled — “Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders.” | concepts[4] |
| concept | superorganism — not defined in this paper's own words; host plus resident microorganisms taken as one entity performing immune and metabolic functions — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions” | concepts[5] |
| concept | diversity — not defined in this paper's own words; the property that characterises a healthy composition in place of a species list - the richer the microbiota, the better it withstands external threats — “Throughout life, the richer and more diverse the microbiota, the better they will withstand external threats. Indeed, gut microbiota represent a changing ecosystem that is severely tested by many factors such as unbalanced diet, stress, antibiotic use, or diseases.” | concepts[6] |
| concept | unique gut microbiota profile — not defined in this paper's own words; individual microbial configuration with host-specific functions — “Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions” | concepts[7] |
| concept | host nutrient metabolism — not defined in this paper's own words; microbiota-supported processing of host nutrients — “Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions” | concepts[8] |
| concept | gut mucosal barrier — not defined in this paper's own words; structural barrier maintained by the microbiota — “Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions” | concepts[9] |
| concept | immunomodulation — not defined in this paper's own words; microbiota regulation of host immunity — “Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions” | concepts[10] |
| concept | protection against pathogens — not defined in this paper's own words; colonization-resistance function of the microbiota — “Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions” | concepts[11] |
| concept | infant transitions — not defined in this paper's own words; birth, feeding, and weaning factors shaping early composition — “Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions” | concepts[12] |
| concept | healthy core native microbiota — not defined in this paper's own words; personal microbiota remaining relatively stable in adulthood — “Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions” | concepts[13] |
| concept | host–microorganism balance — not defined in this paper's own words; balance required for metabolic and immune function — “Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions” | concepts[14] |
| concept | metabolic and immune functions — not defined in this paper's own words; host functions supported by balanced microbiota — “Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions” | concepts[15] |
| concept | cause or consequence — not defined in this paper's own words; causal-direction uncertainty around health-associated balances — “Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions” | concepts[16] |
| concept | human gastrointestinal (GI) tract — not defined in this paper's own words; habitat containing the microbial community — “The human gastrointestinal (GI) tract contains an abundant and diverse microbial community that gathers more than 100 trillion microorganisms [1]. The density of bacterial cells in the colon has been estimated at 1011 to 1012 per milliliter which makes the colon one of the most densely populated microbial habitats known on earth [2]. The gut microbiome encodes over 3 million genes producing thousands of metabolites, whereas the human genome consists of approximately 23,000 genes [3]. For years, scientists have been interested in gut microbiota, but one of the major difficulties in the relevant research has been the ability to culture these microorganisms [4]. During the last years, new technologies have allowed researchers to phylogenetically identify and/or quantify the components of the gut microbiota by analyzing nucleic acids (DNA and RNA) directly extracted from stools. The majority of these techniques are based on the extraction of DNA and the amplification of the 16S ribosomal RNA gene (rRNA) [5, 6]. 16S rRNA sequencing has become the most useful technique to highlight diversity and abundance of the microbiome. The 16S rRNA gene sequences can be exploited with polymerase chain reaction (PCR) and metagenomics sequencing to characterize the microbial strains” | concepts[17] |
| concept | gut microbiome — not defined in this paper's own words; microbial gene complement encoding metabolites — “The human gastrointestinal (GI) tract contains an abundant and diverse microbial community that gathers more than 100 trillion microorganisms [1]. The density of bacterial cells in the colon has been estimated at 1011 to 1012 per milliliter which makes the colon one of the most densely populated microbial habitats known on earth [2]. The gut microbiome encodes over 3 million genes producing thousands of metabolites, whereas the human genome consists of approximately 23,000 genes [3]. For years, scientists have been interested in gut microbiota, but one of the major difficulties in the relevant research has been the ability to culture these microorganisms [4]. During the last years, new technologies have allowed researchers to phylogenetically identify and/or quantify the components of the gut microbiota by analyzing nucleic acids (DNA and RNA) directly extracted from stools. The majority of these techniques are based on the extraction of DNA and the amplification of the 16S ribosomal RNA gene (rRNA) [5, 6]. 16S rRNA sequencing has become the most useful technique to highlight diversity and abundance of the microbiome. The 16S rRNA gene sequences can be exploited with polymerase chain reaction (PCR) and metagenomics sequencing to characterize the microbial strains” | concepts[18] |
| concept | metabolites — not defined in this paper's own words; products encoded by microbial genes — “The human gastrointestinal (GI) tract contains an abundant and diverse microbial community that gathers more than 100 trillion microorganisms [1]. The density of bacterial cells in the colon has been estimated at 1011 to 1012 per milliliter which makes the colon one of the most densely populated microbial habitats known on earth [2]. The gut microbiome encodes over 3 million genes producing thousands of metabolites, whereas the human genome consists of approximately 23,000 genes [3]. For years, scientists have been interested in gut microbiota, but one of the major difficulties in the relevant research has been the ability to culture these microorganisms [4]. During the last years, new technologies have allowed researchers to phylogenetically identify and/or quantify the components of the gut microbiota by analyzing nucleic acids (DNA and RNA) directly extracted from stools. The majority of these techniques are based on the extraction of DNA and the amplification of the 16S ribosomal RNA gene (rRNA) [5, 6]. 16S rRNA sequencing has become the most useful technique to highlight diversity and abundance of the microbiome. The 16S rRNA gene sequences can be exploited with polymerase chain reaction (PCR) and metagenomics sequencing to characterize the microbial strains” | concepts[19] |
| concept | human genome — not defined in this paper's own words; host gene complement contrasted with the microbiome — “The human gastrointestinal (GI) tract contains an abundant and diverse microbial community that gathers more than 100 trillion microorganisms [1]. The density of bacterial cells in the colon has been estimated at 1011 to 1012 per milliliter which makes the colon one of the most densely populated microbial habitats known on earth [2]. The gut microbiome encodes over 3 million genes producing thousands of metabolites, whereas the human genome consists of approximately 23,000 genes [3]. For years, scientists have been interested in gut microbiota, but one of the major difficulties in the relevant research has been the ability to culture these microorganisms [4]. During the last years, new technologies have allowed researchers to phylogenetically identify and/or quantify the components of the gut microbiota by analyzing nucleic acids (DNA and RNA) directly extracted from stools. The majority of these techniques are based on the extraction of DNA and the amplification of the 16S ribosomal RNA gene (rRNA) [5, 6]. 16S rRNA sequencing has become the most useful technique to highlight diversity and abundance of the microbiome. The 16S rRNA gene sequences can be exploited with polymerase chain reaction (PCR) and metagenomics sequencing to characterize the microbial strains” | concepts[20] |
| concept | DNA and RNA — not defined in this paper's own words; nucleic acids extracted directly from stool — “The human gastrointestinal (GI) tract contains an abundant and diverse microbial community that gathers more than 100 trillion microorganisms [1]. The density of bacterial cells in the colon has been estimated at 1011 to 1012 per milliliter which makes the colon one of the most densely populated microbial habitats known on earth [2]. The gut microbiome encodes over 3 million genes producing thousands of metabolites, whereas the human genome consists of approximately 23,000 genes [3]. For years, scientists have been interested in gut microbiota, but one of the major difficulties in the relevant research has been the ability to culture these microorganisms [4]. During the last years, new technologies have allowed researchers to phylogenetically identify and/or quantify the components of the gut microbiota by analyzing nucleic acids (DNA and RNA) directly extracted from stools. The majority of these techniques are based on the extraction of DNA and the amplification of the 16S ribosomal RNA gene (rRNA) [5, 6]. 16S rRNA sequencing has become the most useful technique to highlight diversity and abundance of the microbiome. The 16S rRNA gene sequences can be exploited with polymerase chain reaction (PCR) and metagenomics sequencing to characterize the microbial strains” | concepts[21] |
| concept | 16S ribosomal RNA gene (rRNA) — not defined in this paper's own words; marker amplified to profile community membership — “The human gastrointestinal (GI) tract contains an abundant and diverse microbial community that gathers more than 100 trillion microorganisms [1]. The density of bacterial cells in the colon has been estimated at 1011 to 1012 per milliliter which makes the colon one of the most densely populated microbial habitats known on earth [2]. The gut microbiome encodes over 3 million genes producing thousands of metabolites, whereas the human genome consists of approximately 23,000 genes [3]. For years, scientists have been interested in gut microbiota, but one of the major difficulties in the relevant research has been the ability to culture these microorganisms [4]. During the last years, new technologies have allowed researchers to phylogenetically identify and/or quantify the components of the gut microbiota by analyzing nucleic acids (DNA and RNA) directly extracted from stools. The majority of these techniques are based on the extraction of DNA and the amplification of the 16S ribosomal RNA gene (rRNA) [5, 6]. 16S rRNA sequencing has become the most useful technique to highlight diversity and abundance of the microbiome. The 16S rRNA gene sequences can be exploited with polymerase chain reaction (PCR) and metagenomics sequencing to characterize the microbial strains” | concepts[22] |
| concept | 16S rRNA sequencing — not defined in this paper's own words; technique for highlighting microbiome diversity and abundance — “The human gastrointestinal (GI) tract contains an abundant and diverse microbial community that gathers more than 100 trillion microorganisms [1]. The density of bacterial cells in the colon has been estimated at 1011 to 1012 per milliliter which makes the colon one of the most densely populated microbial habitats known on earth [2]. The gut microbiome encodes over 3 million genes producing thousands of metabolites, whereas the human genome consists of approximately 23,000 genes [3]. For years, scientists have been interested in gut microbiota, but one of the major difficulties in the relevant research has been the ability to culture these microorganisms [4]. During the last years, new technologies have allowed researchers to phylogenetically identify and/or quantify the components of the gut microbiota by analyzing nucleic acids (DNA and RNA) directly extracted from stools. The majority of these techniques are based on the extraction of DNA and the amplification of the 16S ribosomal RNA gene (rRNA) [5, 6]. 16S rRNA sequencing has become the most useful technique to highlight diversity and abundance of the microbiome. The 16S rRNA gene sequences can be exploited with polymerase chain reaction (PCR) and metagenomics sequencing to characterize the microbial strains” | concepts[23] |
| concept | polymerase chain reaction (PCR) — not defined in this paper's own words; amplification method applied to 16S sequences — “The human gastrointestinal (GI) tract contains an abundant and diverse microbial community that gathers more than 100 trillion microorganisms [1]. The density of bacterial cells in the colon has been estimated at 1011 to 1012 per milliliter which makes the colon one of the most densely populated microbial habitats known on earth [2]. The gut microbiome encodes over 3 million genes producing thousands of metabolites, whereas the human genome consists of approximately 23,000 genes [3]. For years, scientists have been interested in gut microbiota, but one of the major difficulties in the relevant research has been the ability to culture these microorganisms [4]. During the last years, new technologies have allowed researchers to phylogenetically identify and/or quantify the components of the gut microbiota by analyzing nucleic acids (DNA and RNA) directly extracted from stools. The majority of these techniques are based on the extraction of DNA and the amplification of the 16S ribosomal RNA gene (rRNA) [5, 6]. 16S rRNA sequencing has become the most useful technique to highlight diversity and abundance of the microbiome. The 16S rRNA gene sequences can be exploited with polymerase chain reaction (PCR) and metagenomics sequencing to characterize the microbial strains” | concepts[24] |
| concept | metagenomics sequencing — not defined in this paper's own words; sequence-based characterization of microbial strains — “The human gastrointestinal (GI) tract contains an abundant and diverse microbial community that gathers more than 100 trillion microorganisms [1]. The density of bacterial cells in the colon has been estimated at 1011 to 1012 per milliliter which makes the colon one of the most densely populated microbial habitats known on earth [2]. The gut microbiome encodes over 3 million genes producing thousands of metabolites, whereas the human genome consists of approximately 23,000 genes [3]. For years, scientists have been interested in gut microbiota, but one of the major difficulties in the relevant research has been the ability to culture these microorganisms [4]. During the last years, new technologies have allowed researchers to phylogenetically identify and/or quantify the components of the gut microbiota by analyzing nucleic acids (DNA and RNA) directly extracted from stools. The majority of these techniques are based on the extraction of DNA and the amplification of the 16S ribosomal RNA gene (rRNA) [5, 6]. 16S rRNA sequencing has become the most useful technique to highlight diversity and abundance of the microbiome. The 16S rRNA gene sequences can be exploited with polymerase chain reaction (PCR) and metagenomics sequencing to characterize the microbial strains” | concepts[25] |
| concept | large diversity — not defined in this paper's own words; community property supporting the superorganism framing — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions [1]. Gut bacteria are key regulators of digestion along the gastrointestinal tract; commensal bacteria play an important role in the extraction, synthesis, and absorption of many nutrients and metabolites, including bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs). Gut microbiota have a crucial immune function against pathogenic bacteria colonization inhibiting their growth, consuming available nutrients and/or producing bacteriocins. Gut microbiota also prevent bacteria invasion by maintaining the intestinal epithelium integrity [10]. Microorganisms prevent pathogenic colonization by many competition processes: nutrient metabolism, pH modification, antimicrobial peptide secretions, and effects on cell signaling pathways. Moreover, recent studies have identified a critical role for commensal bacteria and their products in regulating the development, homeostasis, and function of innate and adaptive immune cells [11]. It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life” | concepts[26] |
| concept | stability and resilience — not defined in this paper's own words; community persistence and recovery properties — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions [1]. Gut bacteria are key regulators of digestion along the gastrointestinal tract; commensal bacteria play an important role in the extraction, synthesis, and absorption of many nutrients and metabolites, including bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs). Gut microbiota have a crucial immune function against pathogenic bacteria colonization inhibiting their growth, consuming available nutrients and/or producing bacteriocins. Gut microbiota also prevent bacteria invasion by maintaining the intestinal epithelium integrity [10]. Microorganisms prevent pathogenic colonization by many competition processes: nutrient metabolism, pH modification, antimicrobial peptide secretions, and effects on cell signaling pathways. Moreover, recent studies have identified a critical role for commensal bacteria and their products in regulating the development, homeostasis, and function of innate and adaptive immune cells [11]. It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life” | concepts[27] |
| concept | symbiotic interaction with the host — not defined in this paper's own words; host-microbe interaction supporting shared function — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions [1]. Gut bacteria are key regulators of digestion along the gastrointestinal tract; commensal bacteria play an important role in the extraction, synthesis, and absorption of many nutrients and metabolites, including bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs). Gut microbiota have a crucial immune function against pathogenic bacteria colonization inhibiting their growth, consuming available nutrients and/or producing bacteriocins. Gut microbiota also prevent bacteria invasion by maintaining the intestinal epithelium integrity [10]. Microorganisms prevent pathogenic colonization by many competition processes: nutrient metabolism, pH modification, antimicrobial peptide secretions, and effects on cell signaling pathways. Moreover, recent studies have identified a critical role for commensal bacteria and their products in regulating the development, homeostasis, and function of innate and adaptive immune cells [11]. It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life” | concepts[28] |
| concept | host and the microorganisms inhabiting it — not defined in this paper's own words; combined entity defined as a superorganism — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions [1]. Gut bacteria are key regulators of digestion along the gastrointestinal tract; commensal bacteria play an important role in the extraction, synthesis, and absorption of many nutrients and metabolites, including bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs). Gut microbiota have a crucial immune function against pathogenic bacteria colonization inhibiting their growth, consuming available nutrients and/or producing bacteriocins. Gut microbiota also prevent bacteria invasion by maintaining the intestinal epithelium integrity [10]. Microorganisms prevent pathogenic colonization by many competition processes: nutrient metabolism, pH modification, antimicrobial peptide secretions, and effects on cell signaling pathways. Moreover, recent studies have identified a critical role for commensal bacteria and their products in regulating the development, homeostasis, and function of innate and adaptive immune cells [11]. It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life” | concepts[29] |
| concept | commensal bacteria — not defined in this paper's own words; resident bacteria extracting nutrients and regulating immunity — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions [1]. Gut bacteria are key regulators of digestion along the gastrointestinal tract; commensal bacteria play an important role in the extraction, synthesis, and absorption of many nutrients and metabolites, including bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs). Gut microbiota have a crucial immune function against pathogenic bacteria colonization inhibiting their growth, consuming available nutrients and/or producing bacteriocins. Gut microbiota also prevent bacteria invasion by maintaining the intestinal epithelium integrity [10]. Microorganisms prevent pathogenic colonization by many competition processes: nutrient metabolism, pH modification, antimicrobial peptide secretions, and effects on cell signaling pathways. Moreover, recent studies have identified a critical role for commensal bacteria and their products in regulating the development, homeostasis, and function of innate and adaptive immune cells [11]. It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life” | concepts[30] |
| concept | short-chain fatty acids (SCFAs) — not defined in this paper's own words; microbial nutrient metabolites — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions [1]. Gut bacteria are key regulators of digestion along the gastrointestinal tract; commensal bacteria play an important role in the extraction, synthesis, and absorption of many nutrients and metabolites, including bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs). Gut microbiota have a crucial immune function against pathogenic bacteria colonization inhibiting their growth, consuming available nutrients and/or producing bacteriocins. Gut microbiota also prevent bacteria invasion by maintaining the intestinal epithelium integrity [10]. Microorganisms prevent pathogenic colonization by many competition processes: nutrient metabolism, pH modification, antimicrobial peptide secretions, and effects on cell signaling pathways. Moreover, recent studies have identified a critical role for commensal bacteria and their products in regulating the development, homeostasis, and function of innate and adaptive immune cells [11]. It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life” | concepts[31] |
| concept | pathogenic bacteria colonization — not defined in this paper's own words; colonization opposed by resident microbiota — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions [1]. Gut bacteria are key regulators of digestion along the gastrointestinal tract; commensal bacteria play an important role in the extraction, synthesis, and absorption of many nutrients and metabolites, including bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs). Gut microbiota have a crucial immune function against pathogenic bacteria colonization inhibiting their growth, consuming available nutrients and/or producing bacteriocins. Gut microbiota also prevent bacteria invasion by maintaining the intestinal epithelium integrity [10]. Microorganisms prevent pathogenic colonization by many competition processes: nutrient metabolism, pH modification, antimicrobial peptide secretions, and effects on cell signaling pathways. Moreover, recent studies have identified a critical role for commensal bacteria and their products in regulating the development, homeostasis, and function of innate and adaptive immune cells [11]. It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life” | concepts[32] |
| concept | intestinal epithelium integrity — not defined in this paper's own words; barrier property maintained by gut microbiota — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions [1]. Gut bacteria are key regulators of digestion along the gastrointestinal tract; commensal bacteria play an important role in the extraction, synthesis, and absorption of many nutrients and metabolites, including bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs). Gut microbiota have a crucial immune function against pathogenic bacteria colonization inhibiting their growth, consuming available nutrients and/or producing bacteriocins. Gut microbiota also prevent bacteria invasion by maintaining the intestinal epithelium integrity [10]. Microorganisms prevent pathogenic colonization by many competition processes: nutrient metabolism, pH modification, antimicrobial peptide secretions, and effects on cell signaling pathways. Moreover, recent studies have identified a critical role for commensal bacteria and their products in regulating the development, homeostasis, and function of innate and adaptive immune cells [11]. It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life” | concepts[33] |
| concept | nutrient metabolism — not defined in this paper's own words; competitive process limiting pathogenic colonization — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions [1]. Gut bacteria are key regulators of digestion along the gastrointestinal tract; commensal bacteria play an important role in the extraction, synthesis, and absorption of many nutrients and metabolites, including bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs). Gut microbiota have a crucial immune function against pathogenic bacteria colonization inhibiting their growth, consuming available nutrients and/or producing bacteriocins. Gut microbiota also prevent bacteria invasion by maintaining the intestinal epithelium integrity [10]. Microorganisms prevent pathogenic colonization by many competition processes: nutrient metabolism, pH modification, antimicrobial peptide secretions, and effects on cell signaling pathways. Moreover, recent studies have identified a critical role for commensal bacteria and their products in regulating the development, homeostasis, and function of innate and adaptive immune cells [11]. It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life” | concepts[34] |
| concept | pH modification — not defined in this paper's own words; competitive environmental change by microorganisms — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions [1]. Gut bacteria are key regulators of digestion along the gastrointestinal tract; commensal bacteria play an important role in the extraction, synthesis, and absorption of many nutrients and metabolites, including bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs). Gut microbiota have a crucial immune function against pathogenic bacteria colonization inhibiting their growth, consuming available nutrients and/or producing bacteriocins. Gut microbiota also prevent bacteria invasion by maintaining the intestinal epithelium integrity [10]. Microorganisms prevent pathogenic colonization by many competition processes: nutrient metabolism, pH modification, antimicrobial peptide secretions, and effects on cell signaling pathways. Moreover, recent studies have identified a critical role for commensal bacteria and their products in regulating the development, homeostasis, and function of innate and adaptive immune cells [11]. It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life” | concepts[35] |
| concept | antimicrobial peptide secretions — not defined in this paper's own words; microbial competition mechanism — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions [1]. Gut bacteria are key regulators of digestion along the gastrointestinal tract; commensal bacteria play an important role in the extraction, synthesis, and absorption of many nutrients and metabolites, including bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs). Gut microbiota have a crucial immune function against pathogenic bacteria colonization inhibiting their growth, consuming available nutrients and/or producing bacteriocins. Gut microbiota also prevent bacteria invasion by maintaining the intestinal epithelium integrity [10]. Microorganisms prevent pathogenic colonization by many competition processes: nutrient metabolism, pH modification, antimicrobial peptide secretions, and effects on cell signaling pathways. Moreover, recent studies have identified a critical role for commensal bacteria and their products in regulating the development, homeostasis, and function of innate and adaptive immune cells [11]. It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life” | concepts[36] |
| concept | cell signaling pathways — not defined in this paper's own words; host pathways affected during colonization resistance — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions [1]. Gut bacteria are key regulators of digestion along the gastrointestinal tract; commensal bacteria play an important role in the extraction, synthesis, and absorption of many nutrients and metabolites, including bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs). Gut microbiota have a crucial immune function against pathogenic bacteria colonization inhibiting their growth, consuming available nutrients and/or producing bacteriocins. Gut microbiota also prevent bacteria invasion by maintaining the intestinal epithelium integrity [10]. Microorganisms prevent pathogenic colonization by many competition processes: nutrient metabolism, pH modification, antimicrobial peptide secretions, and effects on cell signaling pathways. Moreover, recent studies have identified a critical role for commensal bacteria and their products in regulating the development, homeostasis, and function of innate and adaptive immune cells [11]. It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life” | concepts[37] |
| concept | innate and adaptive immune cells — not defined in this paper's own words; immune-cell compartments regulated by commensals — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions [1]. Gut bacteria are key regulators of digestion along the gastrointestinal tract; commensal bacteria play an important role in the extraction, synthesis, and absorption of many nutrients and metabolites, including bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs). Gut microbiota have a crucial immune function against pathogenic bacteria colonization inhibiting their growth, consuming available nutrients and/or producing bacteriocins. Gut microbiota also prevent bacteria invasion by maintaining the intestinal epithelium integrity [10]. Microorganisms prevent pathogenic colonization by many competition processes: nutrient metabolism, pH modification, antimicrobial peptide secretions, and effects on cell signaling pathways. Moreover, recent studies have identified a critical role for commensal bacteria and their products in regulating the development, homeostasis, and function of innate and adaptive immune cells [11]. It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life” | concepts[38] |
| concept | bacteria, yeast, and viruses — not defined in this paper's own words; microorganism groups composing gut microbiota — “Gut microbiota are composed of several species of microorganisms, including bacteria, yeast, and viruses. Taxonomically, bacteria are classified according to phyla, classes, orders, families, genera, and species. Only a few phyla are represented, accounting for more than 160 species [12]. The dominant gut microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia, with the two phyla Firmicutes and Bacteroidetes [13] representing 90% of gut microbiota. The Firmicutes phylum is composed of more than 200 different genera such as Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus. Clostridium genera represent 95% of the Firmicutes phyla. Bacteroidetes consists of predominant genera such as Bacteroides and Prevotella. The Actinobacteria phylum is proportionally less abundant and mainly represented by the Bifidobacterium genus [13]. Examples of taxonomic gut microbiota composition are illustrated” | concepts[39] |
| concept | Firmicutes — not defined in this paper's own words; one of the two dominant gut microbial phyla — “Gut microbiota are composed of several species of microorganisms, including bacteria, yeast, and viruses. Taxonomically, bacteria are classified according to phyla, classes, orders, families, genera, and species. Only a few phyla are represented, accounting for more than 160 species [12]. The dominant gut microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia, with the two phyla Firmicutes and Bacteroidetes [13] representing 90% of gut microbiota. The Firmicutes phylum is composed of more than 200 different genera such as Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus. Clostridium genera represent 95% of the Firmicutes phyla. Bacteroidetes consists of predominant genera such as Bacteroides and Prevotella. The Actinobacteria phylum is proportionally less abundant and mainly represented by the Bifidobacterium genus [13]. Examples of taxonomic gut microbiota composition are illustrated” | concepts[40] |
| concept | Bacteroidetes — not defined in this paper's own words; one of the two dominant gut microbial phyla — “Gut microbiota are composed of several species of microorganisms, including bacteria, yeast, and viruses. Taxonomically, bacteria are classified according to phyla, classes, orders, families, genera, and species. Only a few phyla are represented, accounting for more than 160 species [12]. The dominant gut microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia, with the two phyla Firmicutes and Bacteroidetes [13] representing 90% of gut microbiota. The Firmicutes phylum is composed of more than 200 different genera such as Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus. Clostridium genera represent 95% of the Firmicutes phyla. Bacteroidetes consists of predominant genera such as Bacteroides and Prevotella. The Actinobacteria phylum is proportionally less abundant and mainly represented by the Bifidobacterium genus [13]. Examples of taxonomic gut microbiota composition are illustrated” | concepts[41] |
| concept | Actinobacteria — not defined in this paper's own words; less abundant phylum represented by Bifidobacterium — “Gut microbiota are composed of several species of microorganisms, including bacteria, yeast, and viruses. Taxonomically, bacteria are classified according to phyla, classes, orders, families, genera, and species. Only a few phyla are represented, accounting for more than 160 species [12]. The dominant gut microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia, with the two phyla Firmicutes and Bacteroidetes [13] representing 90% of gut microbiota. The Firmicutes phylum is composed of more than 200 different genera such as Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus. Clostridium genera represent 95% of the Firmicutes phyla. Bacteroidetes consists of predominant genera such as Bacteroides and Prevotella. The Actinobacteria phylum is proportionally less abundant and mainly represented by the Bifidobacterium genus [13]. Examples of taxonomic gut microbiota composition are illustrated” | concepts[42] |
| concept | Proteobacteria — not defined in this paper's own words; gut microbial phylum often enriched in dysbiosis — “Gut microbiota are composed of several species of microorganisms, including bacteria, yeast, and viruses. Taxonomically, bacteria are classified according to phyla, classes, orders, families, genera, and species. Only a few phyla are represented, accounting for more than 160 species [12]. The dominant gut microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia, with the two phyla Firmicutes and Bacteroidetes [13] representing 90% of gut microbiota. The Firmicutes phylum is composed of more than 200 different genera such as Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus. Clostridium genera represent 95% of the Firmicutes phyla. Bacteroidetes consists of predominant genera such as Bacteroides and Prevotella. The Actinobacteria phylum is proportionally less abundant and mainly represented by the Bifidobacterium genus [13]. Examples of taxonomic gut microbiota composition are illustrated” | concepts[43] |
| concept | Fusobacteria — not defined in this paper's own words; gut microbial phylum linked later to colorectal cancer — “Gut microbiota are composed of several species of microorganisms, including bacteria, yeast, and viruses. Taxonomically, bacteria are classified according to phyla, classes, orders, families, genera, and species. Only a few phyla are represented, accounting for more than 160 species [12]. The dominant gut microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia, with the two phyla Firmicutes and Bacteroidetes [13] representing 90% of gut microbiota. The Firmicutes phylum is composed of more than 200 different genera such as Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus. Clostridium genera represent 95% of the Firmicutes phyla. Bacteroidetes consists of predominant genera such as Bacteroides and Prevotella. The Actinobacteria phylum is proportionally less abundant and mainly represented by the Bifidobacterium genus [13]. Examples of taxonomic gut microbiota composition are illustrated” | concepts[44] |
| concept | Verrucomicrobia — not defined in this paper's own words; represented gut microbial phylum — “Gut microbiota are composed of several species of microorganisms, including bacteria, yeast, and viruses. Taxonomically, bacteria are classified according to phyla, classes, orders, families, genera, and species. Only a few phyla are represented, accounting for more than 160 species [12]. The dominant gut microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia, with the two phyla Firmicutes and Bacteroidetes [13] representing 90% of gut microbiota. The Firmicutes phylum is composed of more than 200 different genera such as Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus. Clostridium genera represent 95% of the Firmicutes phyla. Bacteroidetes consists of predominant genera such as Bacteroides and Prevotella. The Actinobacteria phylum is proportionally less abundant and mainly represented by the Bifidobacterium genus [13]. Examples of taxonomic gut microbiota composition are illustrated” | concepts[45] |
| concept | Firmicutes phylum — not defined in this paper's own words; phylum containing more than two hundred genera — “Gut microbiota are composed of several species of microorganisms, including bacteria, yeast, and viruses. Taxonomically, bacteria are classified according to phyla, classes, orders, families, genera, and species. Only a few phyla are represented, accounting for more than 160 species [12]. The dominant gut microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia, with the two phyla Firmicutes and Bacteroidetes [13] representing 90% of gut microbiota. The Firmicutes phylum is composed of more than 200 different genera such as Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus. Clostridium genera represent 95% of the Firmicutes phyla. Bacteroidetes consists of predominant genera such as Bacteroides and Prevotella. The Actinobacteria phylum is proportionally less abundant and mainly represented by the Bifidobacterium genus [13]. Examples of taxonomic gut microbiota composition are illustrated” | concepts[46] |
| concept | Clostridium — not defined in this paper's own words; genus comprising most reported Firmicutes genera — “Gut microbiota are composed of several species of microorganisms, including bacteria, yeast, and viruses. Taxonomically, bacteria are classified according to phyla, classes, orders, families, genera, and species. Only a few phyla are represented, accounting for more than 160 species [12]. The dominant gut microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia, with the two phyla Firmicutes and Bacteroidetes [13] representing 90% of gut microbiota. The Firmicutes phylum is composed of more than 200 different genera such as Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus. Clostridium genera represent 95% of the Firmicutes phyla. Bacteroidetes consists of predominant genera such as Bacteroides and Prevotella. The Actinobacteria phylum is proportionally less abundant and mainly represented by the Bifidobacterium genus [13]. Examples of taxonomic gut microbiota composition are illustrated” | concepts[47] |
| concept | Bacteroides — not defined in this paper's own words; predominant Bacteroidetes genus and enterotype marker — “Gut microbiota are composed of several species of microorganisms, including bacteria, yeast, and viruses. Taxonomically, bacteria are classified according to phyla, classes, orders, families, genera, and species. Only a few phyla are represented, accounting for more than 160 species [12]. The dominant gut microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia, with the two phyla Firmicutes and Bacteroidetes [13] representing 90% of gut microbiota. The Firmicutes phylum is composed of more than 200 different genera such as Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus. Clostridium genera represent 95% of the Firmicutes phyla. Bacteroidetes consists of predominant genera such as Bacteroides and Prevotella. The Actinobacteria phylum is proportionally less abundant and mainly represented by the Bifidobacterium genus [13]. Examples of taxonomic gut microbiota composition are illustrated” | concepts[48] |
| concept | Prevotella — not defined in this paper's own words; predominant Bacteroidetes genus and enterotype marker — “Gut microbiota are composed of several species of microorganisms, including bacteria, yeast, and viruses. Taxonomically, bacteria are classified according to phyla, classes, orders, families, genera, and species. Only a few phyla are represented, accounting for more than 160 species [12]. The dominant gut microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia, with the two phyla Firmicutes and Bacteroidetes [13] representing 90% of gut microbiota. The Firmicutes phylum is composed of more than 200 different genera such as Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus. Clostridium genera represent 95% of the Firmicutes phyla. Bacteroidetes consists of predominant genera such as Bacteroides and Prevotella. The Actinobacteria phylum is proportionally less abundant and mainly represented by the Bifidobacterium genus [13]. Examples of taxonomic gut microbiota composition are illustrated” | concepts[49] |
| concept | Bifidobacterium — not defined in this paper's own words; principal representative of Actinobacteria — “Gut microbiota are composed of several species of microorganisms, including bacteria, yeast, and viruses. Taxonomically, bacteria are classified according to phyla, classes, orders, families, genera, and species. Only a few phyla are represented, accounting for more than 160 species [12]. The dominant gut microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia, with the two phyla Firmicutes and Bacteroidetes [13] representing 90% of gut microbiota. The Firmicutes phylum is composed of more than 200 different genera such as Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus. Clostridium genera represent 95% of the Firmicutes phyla. Bacteroidetes consists of predominant genera such as Bacteroides and Prevotella. The Actinobacteria phylum is proportionally less abundant and mainly represented by the Bifidobacterium genus [13]. Examples of taxonomic gut microbiota composition are illustrated” | concepts[50] |
| concept | small intestine — not defined in this paper's own words; high-bile, short-transit microbial habitat — “Gut microbiota vary according to the intestine anatomical regions, which vary in terms of physiology, pH and O2 tension, digesta flow rates (rapid in the mouth to the caecum, slower afterward), substrate availability, and host secretions [14]. The small intestine provides a more challenging environment for microbial colonizers given the fairly short transit times (3–5 h) and the high bile concentrations. The large intestine, which is characterized by slow flow rates and neutral to mildly acidic pH, harbors by far the largest microbial community (dominated by obligate anaerobic bacteria) [14]. We can observe a microbiota quantitative increasing gradient and a microbiota qualitative decreasing gradient with a progressive aerobic bacteria decrease for the benefit of strictly anaerobic bacteria” | concepts[51] |
| concept | large intestine — not defined in this paper's own words; slow-flow habitat with the largest microbial community — “Gut microbiota vary according to the intestine anatomical regions, which vary in terms of physiology, pH and O2 tension, digesta flow rates (rapid in the mouth to the caecum, slower afterward), substrate availability, and host secretions [14]. The small intestine provides a more challenging environment for microbial colonizers given the fairly short transit times (3–5 h) and the high bile concentrations. The large intestine, which is characterized by slow flow rates and neutral to mildly acidic pH, harbors by far the largest microbial community (dominated by obligate anaerobic bacteria) [14]. We can observe a microbiota quantitative increasing gradient and a microbiota qualitative decreasing gradient with a progressive aerobic bacteria decrease for the benefit of strictly anaerobic bacteria” | concepts[52] |
| concept | obligate anaerobic bacteria — not defined in this paper's own words; dominant organisms in the large intestine — “Gut microbiota vary according to the intestine anatomical regions, which vary in terms of physiology, pH and O2 tension, digesta flow rates (rapid in the mouth to the caecum, slower afterward), substrate availability, and host secretions [14]. The small intestine provides a more challenging environment for microbial colonizers given the fairly short transit times (3–5 h) and the high bile concentrations. The large intestine, which is characterized by slow flow rates and neutral to mildly acidic pH, harbors by far the largest microbial community (dominated by obligate anaerobic bacteria) [14]. We can observe a microbiota quantitative increasing gradient and a microbiota qualitative decreasing gradient with a progressive aerobic bacteria decrease for the benefit of strictly anaerobic bacteria” | concepts[53] |
| concept | transit times — not defined in this paper's own words; anatomical constraint on microbial colonization — “Gut microbiota vary according to the intestine anatomical regions, which vary in terms of physiology, pH and O2 tension, digesta flow rates (rapid in the mouth to the caecum, slower afterward), substrate availability, and host secretions [14]. The small intestine provides a more challenging environment for microbial colonizers given the fairly short transit times (3–5 h) and the high bile concentrations. The large intestine, which is characterized by slow flow rates and neutral to mildly acidic pH, harbors by far the largest microbial community (dominated by obligate anaerobic bacteria) [14]. We can observe a microbiota quantitative increasing gradient and a microbiota qualitative decreasing gradient with a progressive aerobic bacteria decrease for the benefit of strictly anaerobic bacteria” | concepts[54] |
| concept | bile concentrations — not defined in this paper's own words; small-intestine colonization constraint — “Gut microbiota vary according to the intestine anatomical regions, which vary in terms of physiology, pH and O2 tension, digesta flow rates (rapid in the mouth to the caecum, slower afterward), substrate availability, and host secretions [14]. The small intestine provides a more challenging environment for microbial colonizers given the fairly short transit times (3–5 h) and the high bile concentrations. The large intestine, which is characterized by slow flow rates and neutral to mildly acidic pH, harbors by far the largest microbial community (dominated by obligate anaerobic bacteria) [14]. We can observe a microbiota quantitative increasing gradient and a microbiota qualitative decreasing gradient with a progressive aerobic bacteria decrease for the benefit of strictly anaerobic bacteria” | concepts[55] |
| concept | microbiota quantitative increasing gradient — not defined in this paper's own words; increasing microbial quantity along the gut — “Gut microbiota vary according to the intestine anatomical regions, which vary in terms of physiology, pH and O2 tension, digesta flow rates (rapid in the mouth to the caecum, slower afterward), substrate availability, and host secretions [14]. The small intestine provides a more challenging environment for microbial colonizers given the fairly short transit times (3–5 h) and the high bile concentrations. The large intestine, which is characterized by slow flow rates and neutral to mildly acidic pH, harbors by far the largest microbial community (dominated by obligate anaerobic bacteria) [14]. We can observe a microbiota quantitative increasing gradient and a microbiota qualitative decreasing gradient with a progressive aerobic bacteria decrease for the benefit of strictly anaerobic bacteria” | concepts[56] |
| concept | microbiota qualitative decreasing gradient — not defined in this paper's own words; decreasing aerobic share along the gut — “Gut microbiota vary according to the intestine anatomical regions, which vary in terms of physiology, pH and O2 tension, digesta flow rates (rapid in the mouth to the caecum, slower afterward), substrate availability, and host secretions [14]. The small intestine provides a more challenging environment for microbial colonizers given the fairly short transit times (3–5 h) and the high bile concentrations. The large intestine, which is characterized by slow flow rates and neutral to mildly acidic pH, harbors by far the largest microbial community (dominated by obligate anaerobic bacteria) [14]. We can observe a microbiota quantitative increasing gradient and a microbiota qualitative decreasing gradient with a progressive aerobic bacteria decrease for the benefit of strictly anaerobic bacteria” | concepts[57] |
| concept | birth gestational age — not defined in this paper's own words; determinant of neonatal microbiota colonization — “Birth gestational age is a major determinant of gut microbiota colonization. The microbiota composition of preterm infants (<37 weeks of gestation) is different from term counterparts ( Table 1). In preterm infants, after birth, the microbiota colonization is challenged by organ immaturity and environmental factors such as antibiotic use, hospital stay [15], and enteral feeding [16]. For these reasons, the postnatal maturation of gut and systemic immunity may be highly affected by preterm birth [16]. In a new-born pig model, an analysis of the gut microbiota composition of preterm and term pigs showed that Ruminococcus spp., some Enterobacterium spp., Lachnospiraceae, Peptostreptococcaceae, and Clostridiaceae were dominant genera in both preterm and term pigs. However, a higher Enterococcus spp. abundance in preterm than term pigs was found [16]. Preterm infants show low diversity with an increased colonization of potentially pathogenic bacteria from the Enterobacteriaceae family of the Proteobacteria phylum [15] and reduced levels of strict anaerobes such as Bifidobacterium [17], Bacteroides, and _Atopobium” | concepts[58] |
| concept | preterm infants — not defined in this paper's own words; infants whose colonization is challenged by immaturity and care exposures — “Birth gestational age is a major determinant of gut microbiota colonization. The microbiota composition of preterm infants (<37 weeks of gestation) is different from term counterparts ( Table 1). In preterm infants, after birth, the microbiota colonization is challenged by organ immaturity and environmental factors such as antibiotic use, hospital stay [15], and enteral feeding [16]. For these reasons, the postnatal maturation of gut and systemic immunity may be highly affected by preterm birth [16]. In a new-born pig model, an analysis of the gut microbiota composition of preterm and term pigs showed that Ruminococcus spp., some Enterobacterium spp., Lachnospiraceae, Peptostreptococcaceae, and Clostridiaceae were dominant genera in both preterm and term pigs. However, a higher Enterococcus spp. abundance in preterm than term pigs was found [16]. Preterm infants show low diversity with an increased colonization of potentially pathogenic bacteria from the Enterobacteriaceae family of the Proteobacteria phylum [15] and reduced levels of strict anaerobes such as Bifidobacterium [17], Bacteroides, and _Atopobium” | concepts[59] |
| concept | organ immaturity — not defined in this paper's own words; preterm constraint on microbiota colonization — “Birth gestational age is a major determinant of gut microbiota colonization. The microbiota composition of preterm infants (<37 weeks of gestation) is different from term counterparts ( Table 1). In preterm infants, after birth, the microbiota colonization is challenged by organ immaturity and environmental factors such as antibiotic use, hospital stay [15], and enteral feeding [16]. For these reasons, the postnatal maturation of gut and systemic immunity may be highly affected by preterm birth [16]. In a new-born pig model, an analysis of the gut microbiota composition of preterm and term pigs showed that Ruminococcus spp., some Enterobacterium spp., Lachnospiraceae, Peptostreptococcaceae, and Clostridiaceae were dominant genera in both preterm and term pigs. However, a higher Enterococcus spp. abundance in preterm than term pigs was found [16]. Preterm infants show low diversity with an increased colonization of potentially pathogenic bacteria from the Enterobacteriaceae family of the Proteobacteria phylum [15] and reduced levels of strict anaerobes such as Bifidobacterium [17], Bacteroides, and _Atopobium” | concepts[60] |
| concept | postnatal maturation of gut and systemic immunity — not defined in this paper's own words; immune development affected by preterm birth — “Birth gestational age is a major determinant of gut microbiota colonization. The microbiota composition of preterm infants (<37 weeks of gestation) is different from term counterparts ( Table 1). In preterm infants, after birth, the microbiota colonization is challenged by organ immaturity and environmental factors such as antibiotic use, hospital stay [15], and enteral feeding [16]. For these reasons, the postnatal maturation of gut and systemic immunity may be highly affected by preterm birth [16]. In a new-born pig model, an analysis of the gut microbiota composition of preterm and term pigs showed that Ruminococcus spp., some Enterobacterium spp., Lachnospiraceae, Peptostreptococcaceae, and Clostridiaceae were dominant genera in both preterm and term pigs. However, a higher Enterococcus spp. abundance in preterm than term pigs was found [16]. Preterm infants show low diversity with an increased colonization of potentially pathogenic bacteria from the Enterobacteriaceae family of the Proteobacteria phylum [15] and reduced levels of strict anaerobes such as Bifidobacterium [17], Bacteroides, and _Atopobium” | concepts[61] |
| concept | Enterobacteriaceae — not defined in this paper's own words; potentially pathogenic family increased in preterm infants — “Birth gestational age is a major determinant of gut microbiota colonization. The microbiota composition of preterm infants (<37 weeks of gestation) is different from term counterparts ( Table 1). In preterm infants, after birth, the microbiota colonization is challenged by organ immaturity and environmental factors such as antibiotic use, hospital stay [15], and enteral feeding [16]. For these reasons, the postnatal maturation of gut and systemic immunity may be highly affected by preterm birth [16]. In a new-born pig model, an analysis of the gut microbiota composition of preterm and term pigs showed that Ruminococcus spp., some Enterobacterium spp., Lachnospiraceae, Peptostreptococcaceae, and Clostridiaceae were dominant genera in both preterm and term pigs. However, a higher Enterococcus spp. abundance in preterm than term pigs was found [16]. Preterm infants show low diversity with an increased colonization of potentially pathogenic bacteria from the Enterobacteriaceae family of the Proteobacteria phylum [15] and reduced levels of strict anaerobes such as Bifidobacterium [17], Bacteroides, and _Atopobium” | concepts[62] |
| concept | strict anaerobes — not defined in this paper's own words; Bifidobacterium, Bacteroides, and Atopobium reduced in preterm infants — “Birth gestational age is a major determinant of gut microbiota colonization. The microbiota composition of preterm infants (<37 weeks of gestation) is different from term counterparts ( Table 1). In preterm infants, after birth, the microbiota colonization is challenged by organ immaturity and environmental factors such as antibiotic use, hospital stay [15], and enteral feeding [16]. For these reasons, the postnatal maturation of gut and systemic immunity may be highly affected by preterm birth [16]. In a new-born pig model, an analysis of the gut microbiota composition of preterm and term pigs showed that Ruminococcus spp., some Enterobacterium spp., Lachnospiraceae, Peptostreptococcaceae, and Clostridiaceae were dominant genera in both preterm and term pigs. However, a higher Enterococcus spp. abundance in preterm than term pigs was found [16]. Preterm infants show low diversity with an increased colonization of potentially pathogenic bacteria from the Enterobacteriaceae family of the Proteobacteria phylum [15] and reduced levels of strict anaerobes such as Bifidobacterium [17], Bacteroides, and _Atopobium” | concepts[63] |
| concept | human milk oligosaccharides (HMOs) — not defined in this paper's own words; milk components varying with maternal secretor phenotype — “Human milk composition depends on genetic factors and the mother’s secretor and Lewis blood groups defining four phenotypes characterized by different levels of oligosaccharide amounts [18]. Higher levels of Proteobacteria and lower levels of Firmicutes are noted in premature infants of non-secretor mothers [19]. A recent study by Praticò et al. [20] characterizing human breast milk composition demonstrated that human milk oligosaccharides (HMOs) related to different mother phenotypes modulate gut microbiota composition in infants. Specifically, HMOs associated with secretor mothers may have a protective prebiotic effect by decreasing pathogens associated with sepsis and necrotizing enterocolitis (NEC) [19]. This indicates that HMOs may influence the intestinal microbiota and prevent gut dysfunction and NEC in preterm infants” | concepts[64] |
| concept | secretor mothers — not defined in this paper's own words; maternal phenotype associated with protective HMOs — “Human milk composition depends on genetic factors and the mother’s secretor and Lewis blood groups defining four phenotypes characterized by different levels of oligosaccharide amounts [18]. Higher levels of Proteobacteria and lower levels of Firmicutes are noted in premature infants of non-secretor mothers [19]. A recent study by Praticò et al. [20] characterizing human breast milk composition demonstrated that human milk oligosaccharides (HMOs) related to different mother phenotypes modulate gut microbiota composition in infants. Specifically, HMOs associated with secretor mothers may have a protective prebiotic effect by decreasing pathogens associated with sepsis and necrotizing enterocolitis (NEC) [19]. This indicates that HMOs may influence the intestinal microbiota and prevent gut dysfunction and NEC in preterm infants” | concepts[65] |
| concept | protective prebiotic effect — not defined in this paper's own words; possible HMO-mediated decrease of neonatal pathogens — “Human milk composition depends on genetic factors and the mother’s secretor and Lewis blood groups defining four phenotypes characterized by different levels of oligosaccharide amounts [18]. Higher levels of Proteobacteria and lower levels of Firmicutes are noted in premature infants of non-secretor mothers [19]. A recent study by Praticò et al. [20] characterizing human breast milk composition demonstrated that human milk oligosaccharides (HMOs) related to different mother phenotypes modulate gut microbiota composition in infants. Specifically, HMOs associated with secretor mothers may have a protective prebiotic effect by decreasing pathogens associated with sepsis and necrotizing enterocolitis (NEC) [19]. This indicates that HMOs may influence the intestinal microbiota and prevent gut dysfunction and NEC in preterm infants” | concepts[66] |
| concept | necrotizing enterocolitis (NEC) — not defined in this paper's own words; preterm gut disorder potentially prevented by HMO effects — “Human milk composition depends on genetic factors and the mother’s secretor and Lewis blood groups defining four phenotypes characterized by different levels of oligosaccharide amounts [18]. Higher levels of Proteobacteria and lower levels of Firmicutes are noted in premature infants of non-secretor mothers [19]. A recent study by Praticò et al. [20] characterizing human breast milk composition demonstrated that human milk oligosaccharides (HMOs) related to different mother phenotypes modulate gut microbiota composition in infants. Specifically, HMOs associated with secretor mothers may have a protective prebiotic effect by decreasing pathogens associated with sepsis and necrotizing enterocolitis (NEC) [19]. This indicates that HMOs may influence the intestinal microbiota and prevent gut dysfunction and NEC in preterm infants” | concepts[67] |
| concept | sepsis — not defined in this paper's own words; infection outcome associated with HMO-sensitive pathogens — “Human milk composition depends on genetic factors and the mother’s secretor and Lewis blood groups defining four phenotypes characterized by different levels of oligosaccharide amounts [18]. Higher levels of Proteobacteria and lower levels of Firmicutes are noted in premature infants of non-secretor mothers [19]. A recent study by Praticò et al. [20] characterizing human breast milk composition demonstrated that human milk oligosaccharides (HMOs) related to different mother phenotypes modulate gut microbiota composition in infants. Specifically, HMOs associated with secretor mothers may have a protective prebiotic effect by decreasing pathogens associated with sepsis and necrotizing enterocolitis (NEC) [19]. This indicates that HMOs may influence the intestinal microbiota and prevent gut dysfunction and NEC in preterm infants” | concepts[68] |
| concept | Lactoferrin (LF) — not defined in this paper's own words; human-milk component favoring beneficial colonization — “Lactoferrin (LF) is another well-known component of human milk favoring gut infant colonization with beneficial bacteria and consequently representing a crucial role played in preterm infants’ microbiota [22]. Indeed, correlations between LF and beneficial microbiota in breast milk and infant’s feces have been demonstrated [22]. High levels of fecal LF, particularly in preterm infants, may represent an important factor in the initiation, development, and/or composition of the neonatal gut microbiota contributing to the immunologic maturation and well-being of the newborn, especially in preterm infants [22]. Therefore, a mother’s own milk helps to shape developing core gut microbiota that can improve growth and neurodevelopment and decrease the risk of NEC and late-onset sepsis [19, 21]. It is for all these reasons that human milk should be the primary enteral diet of premature infants” | concepts[69] |
| concept | mother’s own milk — not defined in this paper's own words; primary enteral diet proposed for premature infants — “Lactoferrin (LF) is another well-known component of human milk favoring gut infant colonization with beneficial bacteria and consequently representing a crucial role played in preterm infants’ microbiota [22]. Indeed, correlations between LF and beneficial microbiota in breast milk and infant’s feces have been demonstrated [22]. High levels of fecal LF, particularly in preterm infants, may represent an important factor in the initiation, development, and/or composition of the neonatal gut microbiota contributing to the immunologic maturation and well-being of the newborn, especially in preterm infants [22]. Therefore, a mother’s own milk helps to shape developing core gut microbiota that can improve growth and neurodevelopment and decrease the risk of NEC and late-onset sepsis [19, 21]. It is for all these reasons that human milk should be the primary enteral diet of premature infants” | concepts[70] |
| concept | core gut microbiota — not defined in this paper's own words; developing community shaped by maternal milk — “Lactoferrin (LF) is another well-known component of human milk favoring gut infant colonization with beneficial bacteria and consequently representing a crucial role played in preterm infants’ microbiota [22]. Indeed, correlations between LF and beneficial microbiota in breast milk and infant’s feces have been demonstrated [22]. High levels of fecal LF, particularly in preterm infants, may represent an important factor in the initiation, development, and/or composition of the neonatal gut microbiota contributing to the immunologic maturation and well-being of the newborn, especially in preterm infants [22]. Therefore, a mother’s own milk helps to shape developing core gut microbiota that can improve growth and neurodevelopment and decrease the risk of NEC and late-onset sepsis [19, 21]. It is for all these reasons that human milk should be the primary enteral diet of premature infants” | concepts[71] |
| concept | vaginal delivery — not defined in this paper's own words; delivery route transmitting maternal vaginal microbes — “At birth, the intestine is sterile and devoid of bacteria. After birth, a rich and dynamic ecosystem develops from mother’s skin, vaginal and fecal microbiota, and environment microbiota contacts. Microbiota colonization varies according to the type of delivery [23, 24, 25] ( Table 1). With regard to vaginal delivery, newborns acquire a microbiota composition resembling their mother’s vaginal microbiota. Indeed, an analysis of the meconium of newborn infants [24] revealed a strong correlation between the microbiota of the newborn digestive tract and the microbial communities of the mother’s vagina: Lactobacillus, Prevotella, and Sneathia. Biasucci et al. [25] showed that the microbiota of vaginally delivered infants are also characterized by predominant groups such as Bifidobacterium longum and Bifidobacterium catenulatum. Other facultative anaerobic species such as Escherichia coli, Staphylococcus, Bacteroides fragilis, and Streptococcus colonize the infant gut [26, 27, 28]. On the contrary, infants born by cesarean section (C-section) acquire bacteria derived from hospital environment and mother’s skin: Staphylococcus, Corynebacterium, Propionibacterium spp. [24, 29]. Escherichia, Shigella, and Bacteroides species are underrepresented in infants born by cesarean delivery [29]. The intestinal microbiota of neonates delivered by cesarean delivery are less diverse in terms of bacteria species than the microbiota of vaginally delivered infants” | concepts[72] |
| concept | cesarean section (C-section) — not defined in this paper's own words; delivery route transmitting skin and hospital microbes — “At birth, the intestine is sterile and devoid of bacteria. After birth, a rich and dynamic ecosystem develops from mother’s skin, vaginal and fecal microbiota, and environment microbiota contacts. Microbiota colonization varies according to the type of delivery [23, 24, 25] ( Table 1). With regard to vaginal delivery, newborns acquire a microbiota composition resembling their mother’s vaginal microbiota. Indeed, an analysis of the meconium of newborn infants [24] revealed a strong correlation between the microbiota of the newborn digestive tract and the microbial communities of the mother’s vagina: Lactobacillus, Prevotella, and Sneathia. Biasucci et al. [25] showed that the microbiota of vaginally delivered infants are also characterized by predominant groups such as Bifidobacterium longum and Bifidobacterium catenulatum. Other facultative anaerobic species such as Escherichia coli, Staphylococcus, Bacteroides fragilis, and Streptococcus colonize the infant gut [26, 27, 28]. On the contrary, infants born by cesarean section (C-section) acquire bacteria derived from hospital environment and mother’s skin: Staphylococcus, Corynebacterium, Propionibacterium spp. [24, 29]. Escherichia, Shigella, and Bacteroides species are underrepresented in infants born by cesarean delivery [29]. The intestinal microbiota of neonates delivered by cesarean delivery are less diverse in terms of bacteria species than the microbiota of vaginally delivered infants” | concepts[73] |
| concept | mother’s vaginal microbiota — not defined in this paper's own words; source resembled by vaginally delivered infants — “At birth, the intestine is sterile and devoid of bacteria. After birth, a rich and dynamic ecosystem develops from mother’s skin, vaginal and fecal microbiota, and environment microbiota contacts. Microbiota colonization varies according to the type of delivery [23, 24, 25] ( Table 1). With regard to vaginal delivery, newborns acquire a microbiota composition resembling their mother’s vaginal microbiota. Indeed, an analysis of the meconium of newborn infants [24] revealed a strong correlation between the microbiota of the newborn digestive tract and the microbial communities of the mother’s vagina: Lactobacillus, Prevotella, and Sneathia. Biasucci et al. [25] showed that the microbiota of vaginally delivered infants are also characterized by predominant groups such as Bifidobacterium longum and Bifidobacterium catenulatum. Other facultative anaerobic species such as Escherichia coli, Staphylococcus, Bacteroides fragilis, and Streptococcus colonize the infant gut [26, 27, 28]. On the contrary, infants born by cesarean section (C-section) acquire bacteria derived from hospital environment and mother’s skin: Staphylococcus, Corynebacterium, Propionibacterium spp. [24, 29]. Escherichia, Shigella, and Bacteroides species are underrepresented in infants born by cesarean delivery [29]. The intestinal microbiota of neonates delivered by cesarean delivery are less diverse in terms of bacteria species than the microbiota of vaginally delivered infants” | concepts[74] |
| concept | hospital environment — not defined in this paper's own words; source of bacteria after cesarean delivery — “At birth, the intestine is sterile and devoid of bacteria. After birth, a rich and dynamic ecosystem develops from mother’s skin, vaginal and fecal microbiota, and environment microbiota contacts. Microbiota colonization varies according to the type of delivery [23, 24, 25] ( Table 1). With regard to vaginal delivery, newborns acquire a microbiota composition resembling their mother’s vaginal microbiota. Indeed, an analysis of the meconium of newborn infants [24] revealed a strong correlation between the microbiota of the newborn digestive tract and the microbial communities of the mother’s vagina: Lactobacillus, Prevotella, and Sneathia. Biasucci et al. [25] showed that the microbiota of vaginally delivered infants are also characterized by predominant groups such as Bifidobacterium longum and Bifidobacterium catenulatum. Other facultative anaerobic species such as Escherichia coli, Staphylococcus, Bacteroides fragilis, and Streptococcus colonize the infant gut [26, 27, 28]. On the contrary, infants born by cesarean section (C-section) acquire bacteria derived from hospital environment and mother’s skin: Staphylococcus, Corynebacterium, Propionibacterium spp. [24, 29]. Escherichia, Shigella, and Bacteroides species are underrepresented in infants born by cesarean delivery [29]. The intestinal microbiota of neonates delivered by cesarean delivery are less diverse in terms of bacteria species than the microbiota of vaginally delivered infants” | concepts[75] |
| concept | formula-fed infants — not defined in this paper's own words; feeding group with more E. coli, Bacteroides, and C. difficile — “Studies have demonstrated that formula-fed infants are more often colonized with Escherichia coli, Bacteroides, and Clostridium difficile compared with breastfed infants [29, 32]. Regarding Actinobacteria abundance, Bifidobacterium spp. have been associated with breastfeeding and formula milk [33, 34]. However, breastfed infants generally harbor a more complex and diverse Bifidobacterium microbiota than formula-fed infants [34]. Breastfed infants are provided with microbiota having more than a two-fold increase in the number of Bifidobacterium cells compared to formula-fed infants [33]. Breastfed infants have more beneficial gut microbiota, with a higher richness and diversity of Bifidobacterium spp. and a lower number of Clostridium difficile and Escherichia coli than formula-fed infants” | concepts[76] |
| concept | breastfed infants — not defined in this paper's own words; feeding group with richer Bifidobacterium microbiota — “Studies have demonstrated that formula-fed infants are more often colonized with Escherichia coli, Bacteroides, and Clostridium difficile compared with breastfed infants [29, 32]. Regarding Actinobacteria abundance, Bifidobacterium spp. have been associated with breastfeeding and formula milk [33, 34]. However, breastfed infants generally harbor a more complex and diverse Bifidobacterium microbiota than formula-fed infants [34]. Breastfed infants are provided with microbiota having more than a two-fold increase in the number of Bifidobacterium cells compared to formula-fed infants [33]. Breastfed infants have more beneficial gut microbiota, with a higher richness and diversity of Bifidobacterium spp. and a lower number of Clostridium difficile and Escherichia coli than formula-fed infants” | concepts[77] |
| concept | galactooligosaccharide (GOS) — not defined in this paper's own words; breast-milk component fermented by Bifidobacterium — “Bifidobacterium_ spp. are responsible for the fermentation of galactooligosaccharide (GOS), one of the main components of breast milk, to produce SCFAs [35]. Indeed, Bifidobacterium spp. have an enzyme named lacto-N-biosidase, which facilitates the assimilation of GOS [36]. If Bifidobacterium quantity increases, the quantity of HMOs in feces decreases causing elevated acetate and lactate concentrations and decreasing pH [37]; an HMO consumption by Bifidobacteria in the infant’s gut may suggest a prebiotic effect of HMOs on gut infant microbiota by selectively stimulating Bifidobacterium spp. [37]. Another prebiotic effect of β-palmitate, a natural human milk fatty acid and a component of some infant formulas, on gut infant microbiota was demonstrated by positively influencing Bifidobacterium spp. (and Lactobacillus spp.) abundance” | concepts[78] |
| concept | lacto-N-biosidase — not defined in this paper's own words; enzyme facilitating GOS assimilation — “Bifidobacterium_ spp. are responsible for the fermentation of galactooligosaccharide (GOS), one of the main components of breast milk, to produce SCFAs [35]. Indeed, Bifidobacterium spp. have an enzyme named lacto-N-biosidase, which facilitates the assimilation of GOS [36]. If Bifidobacterium quantity increases, the quantity of HMOs in feces decreases causing elevated acetate and lactate concentrations and decreasing pH [37]; an HMO consumption by Bifidobacteria in the infant’s gut may suggest a prebiotic effect of HMOs on gut infant microbiota by selectively stimulating Bifidobacterium spp. [37]. Another prebiotic effect of β-palmitate, a natural human milk fatty acid and a component of some infant formulas, on gut infant microbiota was demonstrated by positively influencing Bifidobacterium spp. (and Lactobacillus spp.) abundance” | concepts[79] |
| concept | HMO consumption — not defined in this paper's own words; selective substrate use proposed as a prebiotic mechanism — “Bifidobacterium_ spp. are responsible for the fermentation of galactooligosaccharide (GOS), one of the main components of breast milk, to produce SCFAs [35]. Indeed, Bifidobacterium spp. have an enzyme named lacto-N-biosidase, which facilitates the assimilation of GOS [36]. If Bifidobacterium quantity increases, the quantity of HMOs in feces decreases causing elevated acetate and lactate concentrations and decreasing pH [37]; an HMO consumption by Bifidobacteria in the infant’s gut may suggest a prebiotic effect of HMOs on gut infant microbiota by selectively stimulating Bifidobacterium spp. [37]. Another prebiotic effect of β-palmitate, a natural human milk fatty acid and a component of some infant formulas, on gut infant microbiota was demonstrated by positively influencing Bifidobacterium spp. (and Lactobacillus spp.) abundance” | concepts[80] |
| concept | β-palmitate — not defined in this paper's own words; human-milk fatty acid with reported prebiotic effect — “Bifidobacterium_ spp. are responsible for the fermentation of galactooligosaccharide (GOS), one of the main components of breast milk, to produce SCFAs [35]. Indeed, Bifidobacterium spp. have an enzyme named lacto-N-biosidase, which facilitates the assimilation of GOS [36]. If Bifidobacterium quantity increases, the quantity of HMOs in feces decreases causing elevated acetate and lactate concentrations and decreasing pH [37]; an HMO consumption by Bifidobacteria in the infant’s gut may suggest a prebiotic effect of HMOs on gut infant microbiota by selectively stimulating Bifidobacterium spp. [37]. Another prebiotic effect of β-palmitate, a natural human milk fatty acid and a component of some infant formulas, on gut infant microbiota was demonstrated by positively influencing Bifidobacterium spp. (and Lactobacillus spp.) abundance” | concepts[81] |
| concept | solid foods — not defined in this paper's own words; weaning exposure coinciding with major community change — “The introduction of solid foods and the termination of milk-feeding/weaning coincide with major gut microbiota changes. The abundance of genera Bifidobacterium, Clostridium coccoides, and Bacteroides are predominant after weaning [40]. The microbiota of breastfed children and the microbiota of children previously fed with formula milk become closer to each other ( Table 1). Dietary habits, infant weaning, and feeding practices become determinants and play a crucial role in gut microbiota variations. The introduction of high-fiber and carbohydrate foods (traditional foods) causes an increase in Firmicutes and Prevotella, whereas the introduction of high-fiber and animal protein foods causes an increase in Bacteroidetes [41]. Furthermore, Fallani et al. [40] demonstrated that northern European countries are associated with a higher proportion of Bifidobacteria in the infant gut microbiota, whereas higher levels of Bacteroides and Lactobacilli characterize southern European countries” | concepts[82] |
| concept | high-fiber and carbohydrate foods — not defined in this paper's own words; weaning diet increasing Firmicutes and Prevotella — “The introduction of solid foods and the termination of milk-feeding/weaning coincide with major gut microbiota changes. The abundance of genera Bifidobacterium, Clostridium coccoides, and Bacteroides are predominant after weaning [40]. The microbiota of breastfed children and the microbiota of children previously fed with formula milk become closer to each other ( Table 1). Dietary habits, infant weaning, and feeding practices become determinants and play a crucial role in gut microbiota variations. The introduction of high-fiber and carbohydrate foods (traditional foods) causes an increase in Firmicutes and Prevotella, whereas the introduction of high-fiber and animal protein foods causes an increase in Bacteroidetes [41]. Furthermore, Fallani et al. [40] demonstrated that northern European countries are associated with a higher proportion of Bifidobacteria in the infant gut microbiota, whereas higher levels of Bacteroides and Lactobacilli characterize southern European countries” | concepts[83] |
| concept | high-fiber and animal protein foods — not defined in this paper's own words; weaning diet increasing Bacteroidetes — “The introduction of solid foods and the termination of milk-feeding/weaning coincide with major gut microbiota changes. The abundance of genera Bifidobacterium, Clostridium coccoides, and Bacteroides are predominant after weaning [40]. The microbiota of breastfed children and the microbiota of children previously fed with formula milk become closer to each other ( Table 1). Dietary habits, infant weaning, and feeding practices become determinants and play a crucial role in gut microbiota variations. The introduction of high-fiber and carbohydrate foods (traditional foods) causes an increase in Firmicutes and Prevotella, whereas the introduction of high-fiber and animal protein foods causes an increase in Bacteroidetes [41]. Furthermore, Fallani et al. [40] demonstrated that northern European countries are associated with a higher proportion of Bifidobacteria in the infant gut microbiota, whereas higher levels of Bacteroides and Lactobacilli characterize southern European countries” | concepts[84] |
| concept | stable adult microbiota composition — not defined in this paper's own words; age-matured composition dominated by three phyla — “Microbiota diversity increases with age until it becomes a stable adult microbiota composition dominated by three bacterial phyla ( Table 1): Firmicutes ( Lachnospiraceae and Ruminococcaceae), Bacteroidetes ( Bacteroidaceae, Prevotellaceae, and Rikenellaceae), and Actinobacteria ( Bifidobacteriaceae and Coriobacteriaceae) that are the result of maturation due to the influence of genetics, environment, diet, lifestyle, and gut physiology [42]. At approximately three years of age, a child’s gut microbiota composition and diversity are most like those of adults [43]. With regard to older people over the age of 70, gut microbiota composition can be affected by digestion and nutrient absorption changes and immune activity weakness. Dietary habit changes (more monotonous) may also weaken gut microbiota diversity. A decrease in anaerobic bacteria such as Bifidobacterium spp. and an increase in Clostridium and Proteobacteria have been observed [44]. Given the role of Bifidobacterium spp. in the stimulation of the immune system and metabolic processes, a Bifidobacteria decrease may partially explain low systemic inflammatory status and malnutrition in older adults” | concepts[85] |
| concept | genetics, environment, diet, lifestyle, and gut physiology — not defined in this paper's own words; drivers of adult microbiota maturation — “Microbiota diversity increases with age until it becomes a stable adult microbiota composition dominated by three bacterial phyla ( Table 1): Firmicutes ( Lachnospiraceae and Ruminococcaceae), Bacteroidetes ( Bacteroidaceae, Prevotellaceae, and Rikenellaceae), and Actinobacteria ( Bifidobacteriaceae and Coriobacteriaceae) that are the result of maturation due to the influence of genetics, environment, diet, lifestyle, and gut physiology [42]. At approximately three years of age, a child’s gut microbiota composition and diversity are most like those of adults [43]. With regard to older people over the age of 70, gut microbiota composition can be affected by digestion and nutrient absorption changes and immune activity weakness. Dietary habit changes (more monotonous) may also weaken gut microbiota diversity. A decrease in anaerobic bacteria such as Bifidobacterium spp. and an increase in Clostridium and Proteobacteria have been observed [44]. Given the role of Bifidobacterium spp. in the stimulation of the immune system and metabolic processes, a Bifidobacteria decrease may partially explain low systemic inflammatory status and malnutrition in older adults” | concepts[86] |
| concept | older people over the age of 70 — not defined in this paper's own words; group with weakened diversity and altered phyla — “Microbiota diversity increases with age until it becomes a stable adult microbiota composition dominated by three bacterial phyla ( Table 1): Firmicutes ( Lachnospiraceae and Ruminococcaceae), Bacteroidetes ( Bacteroidaceae, Prevotellaceae, and Rikenellaceae), and Actinobacteria ( Bifidobacteriaceae and Coriobacteriaceae) that are the result of maturation due to the influence of genetics, environment, diet, lifestyle, and gut physiology [42]. At approximately three years of age, a child’s gut microbiota composition and diversity are most like those of adults [43]. With regard to older people over the age of 70, gut microbiota composition can be affected by digestion and nutrient absorption changes and immune activity weakness. Dietary habit changes (more monotonous) may also weaken gut microbiota diversity. A decrease in anaerobic bacteria such as Bifidobacterium spp. and an increase in Clostridium and Proteobacteria have been observed [44]. Given the role of Bifidobacterium spp. in the stimulation of the immune system and metabolic processes, a Bifidobacteria decrease may partially explain low systemic inflammatory status and malnutrition in older adults” | concepts[87] |
| concept | antibiotic treatments — not defined in this paper's own words; perturbations modifying community composition — “Gut microbiota composition can be more or less affected by antibiotic use. A follow-up study explored the effect of antibiotics with different modes of action on human gut microbiota composition [46] and demonstrated that antibiotic treatments modify the gut microbiota composition with an abundance/appearance of certain species and a decrease/disappearance of other species ( Table 1). Broad-spectrum antibiotics lead to an imbalance between Firmicutes and Bacteroidetes. The bacterial diversity decreases and so does the abundance of these bacteria during the treatments. The alteration of microbiome composition depends on the antibiotic class, dose, period of exposure, pharmacological action, and target bacteria [47] ( Table 1). Specific properties of antibiotics such as antimicrobial effects or mode of action are powerful forces for the selection of intestinal microbiota and are partially responsible for the shifts in bacterial composition during antibiotic therapy” | concepts[88] |
| concept | Broad-spectrum antibiotics — not defined in this paper's own words; antibiotics producing phylum imbalance and diversity loss — “Gut microbiota composition can be more or less affected by antibiotic use. A follow-up study explored the effect of antibiotics with different modes of action on human gut microbiota composition [46] and demonstrated that antibiotic treatments modify the gut microbiota composition with an abundance/appearance of certain species and a decrease/disappearance of other species ( Table 1). Broad-spectrum antibiotics lead to an imbalance between Firmicutes and Bacteroidetes. The bacterial diversity decreases and so does the abundance of these bacteria during the treatments. The alteration of microbiome composition depends on the antibiotic class, dose, period of exposure, pharmacological action, and target bacteria [47] ( Table 1). Specific properties of antibiotics such as antimicrobial effects or mode of action are powerful forces for the selection of intestinal microbiota and are partially responsible for the shifts in bacterial composition during antibiotic therapy” | concepts[89] |
| concept | antibiotic class, dose, period of exposure, pharmacological action, and target bacteria — not defined in this paper's own words; determinants of alteration magnitude — “Gut microbiota composition can be more or less affected by antibiotic use. A follow-up study explored the effect of antibiotics with different modes of action on human gut microbiota composition [46] and demonstrated that antibiotic treatments modify the gut microbiota composition with an abundance/appearance of certain species and a decrease/disappearance of other species ( Table 1). Broad-spectrum antibiotics lead to an imbalance between Firmicutes and Bacteroidetes. The bacterial diversity decreases and so does the abundance of these bacteria during the treatments. The alteration of microbiome composition depends on the antibiotic class, dose, period of exposure, pharmacological action, and target bacteria [47] ( Table 1). Specific properties of antibiotics such as antimicrobial effects or mode of action are powerful forces for the selection of intestinal microbiota and are partially responsible for the shifts in bacterial composition during antibiotic therapy” | concepts[90] |
| concept | memory of past disturbance — not defined in this paper's own words; lasting state retained after antibiotic exposure — “A cultivation-independent survey of gut microbiota composition of three persons before, during, and after two exposures to the same antibiotic (ciprofloxacin) [48] has been conducted. This study revealed a considerable resilience to antibiotic administration but also suggested that, in some cases, the system retains a memory of past disturbance and that, in all cases, repeated disturbance leads to a persistent regime shift [48]. The impact of antibiotic disturbance on the resilience of microbiota during future antibiotic treatments can thus also vary considerably across individuals” | concepts[91] |
| concept | persistent regime shift — not defined in this paper's own words; long-term state following repeated disturbance — “A cultivation-independent survey of gut microbiota composition of three persons before, during, and after two exposures to the same antibiotic (ciprofloxacin) [48] has been conducted. This study revealed a considerable resilience to antibiotic administration but also suggested that, in some cases, the system retains a memory of past disturbance and that, in all cases, repeated disturbance leads to a persistent regime shift [48]. The impact of antibiotic disturbance on the resilience of microbiota during future antibiotic treatments can thus also vary considerably across individuals” | concepts[92] |
| concept | inter-individual variations — not defined in this paper's own words; differences between individuals — “We highlighted that the gut microbiota composition varies in the same individual and we will see that it also changes between individuals. These inter-individual variations are principally due to enterotypes, body mass index (BMI) level, and external factors such as lifestyle, exercise frequency, ethnicity, and dietary and cultural habits. The microbiota abundance variations between individuals are illustrated in Table 2” | concepts[93] |
| concept | intra-individual variations — not defined in this paper's own words; changes within an individual over life — “Considering the characteristics of gut microbiota such as the large diversity, the stability and resilience, and the symbiotic interaction with the host, we can define the host and the microorganisms inhabiting it as a “superorganism” [8, 9] which performs immune and metabolic functions [1]. Gut bacteria are key regulators of digestion along the gastrointestinal tract; commensal bacteria play an important role in the extraction, synthesis, and absorption of many nutrients and metabolites, including bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs). Gut microbiota have a crucial immune function against pathogenic bacteria colonization inhibiting their growth, consuming available nutrients and/or producing bacteriocins. Gut microbiota also prevent bacteria invasion by maintaining the intestinal epithelium integrity [10]. Microorganisms prevent pathogenic colonization by many competition processes: nutrient metabolism, pH modification, antimicrobial peptide secretions, and effects on cell signaling pathways. Moreover, recent studies have identified a critical role for commensal bacteria and their products in regulating the development, homeostasis, and function of innate and adaptive immune cells [11]. It is paradoxical to note that the gut microbiota functions are highly preserved between individuals, whereas each individual’s gut microbiota are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variations throughout human life” | concepts[94] |
| concept | enterotype I — not defined in this paper's own words; Bacteroides-dominated enterotype — “Gut microbiota of each individual are specifically characterized by clusters of bacteria named enterotypes [13]. Three enterotypes are characterized by three dominant bacteria clusters ( Table 2): Bacteroides (enterotype I), Prevotella (enterotype II), or Ruminococcus (enterotype III). Each enterotype harbors different bacteria genera ( Table 1). These three enterotypes are not only enumerations of bacteria; they are also specifically regrouped by functions. Indeed, an enterotype is a functional harmonious association of several bacteria species rather than a systematic addition of bacteria species. Every enterotype is not a clear-cut identity such as blood groups; however, enterotypes characterize individuals, remain stable from adulthood, and can be restored if they are modified. Each enterotype with its distinctive clusters of bacteria and respective functional characteristics defines a distinctive way of generating energy from fermentable substrates available in the colon. Indeed, bacteria clusters of enterotype I derive energy primarily from carbohydrates using principally glycolysis and pentose phosphate pathways, whereas bacteria clusters of enterotypes II and III are able to degrade mucin glycoproteins of the gut mucosal layer. Enterotypes seem to be principally defined according to dietary habits. Understanding the origins and functions of enterotypes may improve the knowledge of the relationships between gut microbiota and human health” | concepts[95] |
| concept | enterotype II — not defined in this paper's own words; Prevotella-dominated enterotype — “Gut microbiota of each individual are specifically characterized by clusters of bacteria named enterotypes [13]. Three enterotypes are characterized by three dominant bacteria clusters ( Table 2): Bacteroides (enterotype I), Prevotella (enterotype II), or Ruminococcus (enterotype III). Each enterotype harbors different bacteria genera ( Table 1). These three enterotypes are not only enumerations of bacteria; they are also specifically regrouped by functions. Indeed, an enterotype is a functional harmonious association of several bacteria species rather than a systematic addition of bacteria species. Every enterotype is not a clear-cut identity such as blood groups; however, enterotypes characterize individuals, remain stable from adulthood, and can be restored if they are modified. Each enterotype with its distinctive clusters of bacteria and respective functional characteristics defines a distinctive way of generating energy from fermentable substrates available in the colon. Indeed, bacteria clusters of enterotype I derive energy primarily from carbohydrates using principally glycolysis and pentose phosphate pathways, whereas bacteria clusters of enterotypes II and III are able to degrade mucin glycoproteins of the gut mucosal layer. Enterotypes seem to be principally defined according to dietary habits. Understanding the origins and functions of enterotypes may improve the knowledge of the relationships between gut microbiota and human health” | concepts[96] |
| concept | enterotype III — not defined in this paper's own words; Ruminococcus-dominated enterotype — “Gut microbiota of each individual are specifically characterized by clusters of bacteria named enterotypes [13]. Three enterotypes are characterized by three dominant bacteria clusters ( Table 2): Bacteroides (enterotype I), Prevotella (enterotype II), or Ruminococcus (enterotype III). Each enterotype harbors different bacteria genera ( Table 1). These three enterotypes are not only enumerations of bacteria; they are also specifically regrouped by functions. Indeed, an enterotype is a functional harmonious association of several bacteria species rather than a systematic addition of bacteria species. Every enterotype is not a clear-cut identity such as blood groups; however, enterotypes characterize individuals, remain stable from adulthood, and can be restored if they are modified. Each enterotype with its distinctive clusters of bacteria and respective functional characteristics defines a distinctive way of generating energy from fermentable substrates available in the colon. Indeed, bacteria clusters of enterotype I derive energy primarily from carbohydrates using principally glycolysis and pentose phosphate pathways, whereas bacteria clusters of enterotypes II and III are able to degrade mucin glycoproteins of the gut mucosal layer. Enterotypes seem to be principally defined according to dietary habits. Understanding the origins and functions of enterotypes may improve the knowledge of the relationships between gut microbiota and human health” | concepts[97] |
| concept | fermentable substrates — not defined in this paper's own words; colon substrates whose energy extraction differs by enterotype — “Gut microbiota of each individual are specifically characterized by clusters of bacteria named enterotypes [13]. Three enterotypes are characterized by three dominant bacteria clusters ( Table 2): Bacteroides (enterotype I), Prevotella (enterotype II), or Ruminococcus (enterotype III). Each enterotype harbors different bacteria genera ( Table 1). These three enterotypes are not only enumerations of bacteria; they are also specifically regrouped by functions. Indeed, an enterotype is a functional harmonious association of several bacteria species rather than a systematic addition of bacteria species. Every enterotype is not a clear-cut identity such as blood groups; however, enterotypes characterize individuals, remain stable from adulthood, and can be restored if they are modified. Each enterotype with its distinctive clusters of bacteria and respective functional characteristics defines a distinctive way of generating energy from fermentable substrates available in the colon. Indeed, bacteria clusters of enterotype I derive energy primarily from carbohydrates using principally glycolysis and pentose phosphate pathways, whereas bacteria clusters of enterotypes II and III are able to degrade mucin glycoproteins of the gut mucosal layer. Enterotypes seem to be principally defined according to dietary habits. Understanding the origins and functions of enterotypes may improve the knowledge of the relationships between gut microbiota and human health” | concepts[98] |
| concept | glycolysis and pentose phosphate pathways — not defined in this paper's own words; carbohydrate-energy pathways emphasized for enterotype I — “Gut microbiota of each individual are specifically characterized by clusters of bacteria named enterotypes [13]. Three enterotypes are characterized by three dominant bacteria clusters ( Table 2): Bacteroides (enterotype I), Prevotella (enterotype II), or Ruminococcus (enterotype III). Each enterotype harbors different bacteria genera ( Table 1). These three enterotypes are not only enumerations of bacteria; they are also specifically regrouped by functions. Indeed, an enterotype is a functional harmonious association of several bacteria species rather than a systematic addition of bacteria species. Every enterotype is not a clear-cut identity such as blood groups; however, enterotypes characterize individuals, remain stable from adulthood, and can be restored if they are modified. Each enterotype with its distinctive clusters of bacteria and respective functional characteristics defines a distinctive way of generating energy from fermentable substrates available in the colon. Indeed, bacteria clusters of enterotype I derive energy primarily from carbohydrates using principally glycolysis and pentose phosphate pathways, whereas bacteria clusters of enterotypes II and III are able to degrade mucin glycoproteins of the gut mucosal layer. Enterotypes seem to be principally defined according to dietary habits. Understanding the origins and functions of enterotypes may improve the knowledge of the relationships between gut microbiota and human health” | concepts[99] |
| concept | mucin glycoproteins — not defined in this paper's own words; gut-layer substrates degraded by enterotypes II and III — “Gut microbiota of each individual are specifically characterized by clusters of bacteria named enterotypes [13]. Three enterotypes are characterized by three dominant bacteria clusters ( Table 2): Bacteroides (enterotype I), Prevotella (enterotype II), or Ruminococcus (enterotype III). Each enterotype harbors different bacteria genera ( Table 1). These three enterotypes are not only enumerations of bacteria; they are also specifically regrouped by functions. Indeed, an enterotype is a functional harmonious association of several bacteria species rather than a systematic addition of bacteria species. Every enterotype is not a clear-cut identity such as blood groups; however, enterotypes characterize individuals, remain stable from adulthood, and can be restored if they are modified. Each enterotype with its distinctive clusters of bacteria and respective functional characteristics defines a distinctive way of generating energy from fermentable substrates available in the colon. Indeed, bacteria clusters of enterotype I derive energy primarily from carbohydrates using principally glycolysis and pentose phosphate pathways, whereas bacteria clusters of enterotypes II and III are able to degrade mucin glycoproteins of the gut mucosal layer. Enterotypes seem to be principally defined according to dietary habits. Understanding the origins and functions of enterotypes may improve the knowledge of the relationships between gut microbiota and human health” | concepts[100] |
| concept | dietary habits — not defined in this paper's own words; principal proposed determinant of enterotypes — “Gut microbiota of each individual are specifically characterized by clusters of bacteria named enterotypes [13]. Three enterotypes are characterized by three dominant bacteria clusters ( Table 2): Bacteroides (enterotype I), Prevotella (enterotype II), or Ruminococcus (enterotype III). Each enterotype harbors different bacteria genera ( Table 1). These three enterotypes are not only enumerations of bacteria; they are also specifically regrouped by functions. Indeed, an enterotype is a functional harmonious association of several bacteria species rather than a systematic addition of bacteria species. Every enterotype is not a clear-cut identity such as blood groups; however, enterotypes characterize individuals, remain stable from adulthood, and can be restored if they are modified. Each enterotype with its distinctive clusters of bacteria and respective functional characteristics defines a distinctive way of generating energy from fermentable substrates available in the colon. Indeed, bacteria clusters of enterotype I derive energy primarily from carbohydrates using principally glycolysis and pentose phosphate pathways, whereas bacteria clusters of enterotypes II and III are able to degrade mucin glycoproteins of the gut mucosal layer. Enterotypes seem to be principally defined according to dietary habits. Understanding the origins and functions of enterotypes may improve the knowledge of the relationships between gut microbiota and human health” | concepts[101] |
| concept | Firmicutes-to-Bacteroidetes ratio — not defined in this paper's own words; community ratio elevated in obese children — “have examined the impact of childhood BMI on gut microbiota composition and demonstrated that children with overweight or normal BMI are provided with a higher microbial diversity than underweight children. Gut microbiota diversity descends stepwise based on BMI class [50, 52]. Bervoets et al. [53] demonstrated that the microbiota of obese children are provided with an elevated Firmicutes-to-Bacteroidetes ratio compared to the microbiota of lean children [53]. Furthermore, low relative proportions of Bifidobacterium vulgatus and high concentrations of Lactobacillus spp. are observed in the obese microbiota [53]. Riva et al. [54] confirmed that obesity is associated with elevated levels of Firmicutes such as Ruminococcaceae and depleted levels of Bacteroidetes such as Bacteroidaceae and Bacteroides. SCFAs are higher in obese children suggesting elevated substrate utilization. These findings suggest that the dysbiosis of gut microbiota may contribute to the pathophysiology of obesity and the increased ratio of Firmicutes to Bacteroidetes is associated with the increased production of SCFAs and energy harvest from colonic fermentation [54]. The underweight BMI level also revealed profound gut microbiota variations. Borgo et al. [55] performed a comprehensive data analysis comparing gut microbiota and anthropometric traits of 15 anorexia nervosa (AN) women and healthy controls. Results showed that AN intestinal microbiota showed a significant increase in Enterobacteriaceae and Methanobrevibacter smithii compared with healthy controls [55]. On the contrary, the genera Roseburia, Ruminococcus, and Clostridium were depleted in line with the observed reduction in AN of the total SCFAs [55]. BMI levels represent a valid predictive value for gut microbiota dysbiosis. Studies have demonstrated that gut microbiota variations are correlated with increased or depleted production of SCFAs that may respectively contribute to the pathophysiology of obesity or AN. Interventions such as prebiotics and probiotics may be possible solutions to manage both pediatric obesity” | concepts[102] |
| concept | energy harvest from colonic fermentation — not defined in this paper's own words; energy-yield pathway associated with obesity — “have examined the impact of childhood BMI on gut microbiota composition and demonstrated that children with overweight or normal BMI are provided with a higher microbial diversity than underweight children. Gut microbiota diversity descends stepwise based on BMI class [50, 52]. Bervoets et al. [53] demonstrated that the microbiota of obese children are provided with an elevated Firmicutes-to-Bacteroidetes ratio compared to the microbiota of lean children [53]. Furthermore, low relative proportions of Bifidobacterium vulgatus and high concentrations of Lactobacillus spp. are observed in the obese microbiota [53]. Riva et al. [54] confirmed that obesity is associated with elevated levels of Firmicutes such as Ruminococcaceae and depleted levels of Bacteroidetes such as Bacteroidaceae and Bacteroides. SCFAs are higher in obese children suggesting elevated substrate utilization. These findings suggest that the dysbiosis of gut microbiota may contribute to the pathophysiology of obesity and the increased ratio of Firmicutes to Bacteroidetes is associated with the increased production of SCFAs and energy harvest from colonic fermentation [54]. The underweight BMI level also revealed profound gut microbiota variations. Borgo et al. [55] performed a comprehensive data analysis comparing gut microbiota and anthropometric traits of 15 anorexia nervosa (AN) women and healthy controls. Results showed that AN intestinal microbiota showed a significant increase in Enterobacteriaceae and Methanobrevibacter smithii compared with healthy controls [55]. On the contrary, the genera Roseburia, Ruminococcus, and Clostridium were depleted in line with the observed reduction in AN of the total SCFAs [55]. BMI levels represent a valid predictive value for gut microbiota dysbiosis. Studies have demonstrated that gut microbiota variations are correlated with increased or depleted production of SCFAs that may respectively contribute to the pathophysiology of obesity or AN. Interventions such as prebiotics and probiotics may be possible solutions to manage both pediatric obesity” | concepts[103] |
| concept | anorexia nervosa (AN) — not defined in this paper's own words; underweight condition with altered microbiota and SCFAs — “have examined the impact of childhood BMI on gut microbiota composition and demonstrated that children with overweight or normal BMI are provided with a higher microbial diversity than underweight children. Gut microbiota diversity descends stepwise based on BMI class [50, 52]. Bervoets et al. [53] demonstrated that the microbiota of obese children are provided with an elevated Firmicutes-to-Bacteroidetes ratio compared to the microbiota of lean children [53]. Furthermore, low relative proportions of Bifidobacterium vulgatus and high concentrations of Lactobacillus spp. are observed in the obese microbiota [53]. Riva et al. [54] confirmed that obesity is associated with elevated levels of Firmicutes such as Ruminococcaceae and depleted levels of Bacteroidetes such as Bacteroidaceae and Bacteroides. SCFAs are higher in obese children suggesting elevated substrate utilization. These findings suggest that the dysbiosis of gut microbiota may contribute to the pathophysiology of obesity and the increased ratio of Firmicutes to Bacteroidetes is associated with the increased production of SCFAs and energy harvest from colonic fermentation [54]. The underweight BMI level also revealed profound gut microbiota variations. Borgo et al. [55] performed a comprehensive data analysis comparing gut microbiota and anthropometric traits of 15 anorexia nervosa (AN) women and healthy controls. Results showed that AN intestinal microbiota showed a significant increase in Enterobacteriaceae and Methanobrevibacter smithii compared with healthy controls [55]. On the contrary, the genera Roseburia, Ruminococcus, and Clostridium were depleted in line with the observed reduction in AN of the total SCFAs [55]. BMI levels represent a valid predictive value for gut microbiota dysbiosis. Studies have demonstrated that gut microbiota variations are correlated with increased or depleted production of SCFAs that may respectively contribute to the pathophysiology of obesity or AN. Interventions such as prebiotics and probiotics may be possible solutions to manage both pediatric obesity” | concepts[104] |
| concept | prebiotics and probiotics — not defined in this paper's own words; candidate interventions for pediatric obesity and anorexia — “have examined the impact of childhood BMI on gut microbiota composition and demonstrated that children with overweight or normal BMI are provided with a higher microbial diversity than underweight children. Gut microbiota diversity descends stepwise based on BMI class [50, 52]. Bervoets et al. [53] demonstrated that the microbiota of obese children are provided with an elevated Firmicutes-to-Bacteroidetes ratio compared to the microbiota of lean children [53]. Furthermore, low relative proportions of Bifidobacterium vulgatus and high concentrations of Lactobacillus spp. are observed in the obese microbiota [53]. Riva et al. [54] confirmed that obesity is associated with elevated levels of Firmicutes such as Ruminococcaceae and depleted levels of Bacteroidetes such as Bacteroidaceae and Bacteroides. SCFAs are higher in obese children suggesting elevated substrate utilization. These findings suggest that the dysbiosis of gut microbiota may contribute to the pathophysiology of obesity and the increased ratio of Firmicutes to Bacteroidetes is associated with the increased production of SCFAs and energy harvest from colonic fermentation [54]. The underweight BMI level also revealed profound gut microbiota variations. Borgo et al. [55] performed a comprehensive data analysis comparing gut microbiota and anthropometric traits of 15 anorexia nervosa (AN) women and healthy controls. Results showed that AN intestinal microbiota showed a significant increase in Enterobacteriaceae and Methanobrevibacter smithii compared with healthy controls [55]. On the contrary, the genera Roseburia, Ruminococcus, and Clostridium were depleted in line with the observed reduction in AN of the total SCFAs [55]. BMI levels represent a valid predictive value for gut microbiota dysbiosis. Studies have demonstrated that gut microbiota variations are correlated with increased or depleted production of SCFAs that may respectively contribute to the pathophysiology of obesity or AN. Interventions such as prebiotics and probiotics may be possible solutions to manage both pediatric obesity” | concepts[105] |
| concept | Western diet — not defined in this paper's own words; high-fat and animal-protein diet linked to Bacteroides enterotype — “While the microbiome of a healthy individual is relatively stable, gut microbial dynamics can certainly be influenced by lifestyle and dietary cultural choices [56]. A study of European children (fed with the Western diet) and Burkina Faso children (assuming a diet rich in millet/sorghum + local vegetables containing very few lipids and animal proteins) [57] revealed that African children’s microbiota have a remarkable abundance of Prevotella and Xylanibacter. Furthermore, Shigella and Escherichia are widely under-represented. Another study [58] compared Hadza hunter-gatherers and Italian gut microbiota. At the phylum level, Hadza gut microbiota are largely enriched in Proteobacteria and Spirochaetes, which are extremely rare in the Italian gut microbiota, whereas Actinobacteria, an important subdominant component of the Italian gut microbiota, are almost absent. At the genus level, Hadza gut microbiota are comparatively enriched in Prevotella, Eubacterium, Oscillibacter, Butyricicoccus, Sporobacter, Succinivibrio, and Treponema and correspondingly depleted in Bifidobacterium, Bacteroides, Blautia, Dorea, unclassified Lachnospiraceae, Roseburia, Faecalibacterium, Ruminococcus, and unclassified Erysipelotrichaceae. These two studies showed that African gut microbiota have clearly an enterotype Prevotella (enterotype II); the African diet rich in millet/sorghum + local vegetables containing very few lipids and animal proteins allows a mucine degradation in synergy with Desulfovibrionaceae. European gut microbiota (Western diet) have principally an enterotype Bacteroides (enterotype I): the European diet rich in lipids and animal proteins allows energy production from carbohydrates and proteins through fermentation [13]. David et al. [59] compared plant-based diet microbiome (high fibers and low fats and proteins) with animal-based diet microbiome (low fibers and high fats and proteins) and respective changes in microbiome on either diet and demonstrated that a shift toward an animal-based diet increases the abundance of bile-tolerant microorganisms ( Alistipes, Bilophila, and Bacteroides) and decreases the levels of Firmicutes that metabolize dietary plant polysaccharides ( Roseburia, Eubacterium rectale, and Ruminococcus bromii). Moreover, microbial activity trades off between carbohydrate and protein fermentation when the type of diet respectively changes. This change occurred only one day after the diet reached the distal gut microbiota. David et al. [59] showed that diet alters human microbiota rapidly and reproducibly” | concepts[106] |
| concept | African diet — not defined in this paper's own words; fiber-rich diet linked to Prevotella enterotype — “While the microbiome of a healthy individual is relatively stable, gut microbial dynamics can certainly be influenced by lifestyle and dietary cultural choices [56]. A study of European children (fed with the Western diet) and Burkina Faso children (assuming a diet rich in millet/sorghum + local vegetables containing very few lipids and animal proteins) [57] revealed that African children’s microbiota have a remarkable abundance of Prevotella and Xylanibacter. Furthermore, Shigella and Escherichia are widely under-represented. Another study [58] compared Hadza hunter-gatherers and Italian gut microbiota. At the phylum level, Hadza gut microbiota are largely enriched in Proteobacteria and Spirochaetes, which are extremely rare in the Italian gut microbiota, whereas Actinobacteria, an important subdominant component of the Italian gut microbiota, are almost absent. At the genus level, Hadza gut microbiota are comparatively enriched in Prevotella, Eubacterium, Oscillibacter, Butyricicoccus, Sporobacter, Succinivibrio, and Treponema and correspondingly depleted in Bifidobacterium, Bacteroides, Blautia, Dorea, unclassified Lachnospiraceae, Roseburia, Faecalibacterium, Ruminococcus, and unclassified Erysipelotrichaceae. These two studies showed that African gut microbiota have clearly an enterotype Prevotella (enterotype II); the African diet rich in millet/sorghum + local vegetables containing very few lipids and animal proteins allows a mucine degradation in synergy with Desulfovibrionaceae. European gut microbiota (Western diet) have principally an enterotype Bacteroides (enterotype I): the European diet rich in lipids and animal proteins allows energy production from carbohydrates and proteins through fermentation [13]. David et al. [59] compared plant-based diet microbiome (high fibers and low fats and proteins) with animal-based diet microbiome (low fibers and high fats and proteins) and respective changes in microbiome on either diet and demonstrated that a shift toward an animal-based diet increases the abundance of bile-tolerant microorganisms ( Alistipes, Bilophila, and Bacteroides) and decreases the levels of Firmicutes that metabolize dietary plant polysaccharides ( Roseburia, Eubacterium rectale, and Ruminococcus bromii). Moreover, microbial activity trades off between carbohydrate and protein fermentation when the type of diet respectively changes. This change occurred only one day after the diet reached the distal gut microbiota. David et al. [59] showed that diet alters human microbiota rapidly and reproducibly” | concepts[107] |
| concept | plant-based diet microbiome — not defined in this paper's own words; high-fiber, low-fat/protein dietary community — “While the microbiome of a healthy individual is relatively stable, gut microbial dynamics can certainly be influenced by lifestyle and dietary cultural choices [56]. A study of European children (fed with the Western diet) and Burkina Faso children (assuming a diet rich in millet/sorghum + local vegetables containing very few lipids and animal proteins) [57] revealed that African children’s microbiota have a remarkable abundance of Prevotella and Xylanibacter. Furthermore, Shigella and Escherichia are widely under-represented. Another study [58] compared Hadza hunter-gatherers and Italian gut microbiota. At the phylum level, Hadza gut microbiota are largely enriched in Proteobacteria and Spirochaetes, which are extremely rare in the Italian gut microbiota, whereas Actinobacteria, an important subdominant component of the Italian gut microbiota, are almost absent. At the genus level, Hadza gut microbiota are comparatively enriched in Prevotella, Eubacterium, Oscillibacter, Butyricicoccus, Sporobacter, Succinivibrio, and Treponema and correspondingly depleted in Bifidobacterium, Bacteroides, Blautia, Dorea, unclassified Lachnospiraceae, Roseburia, Faecalibacterium, Ruminococcus, and unclassified Erysipelotrichaceae. These two studies showed that African gut microbiota have clearly an enterotype Prevotella (enterotype II); the African diet rich in millet/sorghum + local vegetables containing very few lipids and animal proteins allows a mucine degradation in synergy with Desulfovibrionaceae. European gut microbiota (Western diet) have principally an enterotype Bacteroides (enterotype I): the European diet rich in lipids and animal proteins allows energy production from carbohydrates and proteins through fermentation [13]. David et al. [59] compared plant-based diet microbiome (high fibers and low fats and proteins) with animal-based diet microbiome (low fibers and high fats and proteins) and respective changes in microbiome on either diet and demonstrated that a shift toward an animal-based diet increases the abundance of bile-tolerant microorganisms ( Alistipes, Bilophila, and Bacteroides) and decreases the levels of Firmicutes that metabolize dietary plant polysaccharides ( Roseburia, Eubacterium rectale, and Ruminococcus bromii). Moreover, microbial activity trades off between carbohydrate and protein fermentation when the type of diet respectively changes. This change occurred only one day after the diet reached the distal gut microbiota. David et al. [59] showed that diet alters human microbiota rapidly and reproducibly” | concepts[108] |
| concept | animal-based diet microbiome — not defined in this paper's own words; low-fiber, high-fat/protein dietary community — “While the microbiome of a healthy individual is relatively stable, gut microbial dynamics can certainly be influenced by lifestyle and dietary cultural choices [56]. A study of European children (fed with the Western diet) and Burkina Faso children (assuming a diet rich in millet/sorghum + local vegetables containing very few lipids and animal proteins) [57] revealed that African children’s microbiota have a remarkable abundance of Prevotella and Xylanibacter. Furthermore, Shigella and Escherichia are widely under-represented. Another study [58] compared Hadza hunter-gatherers and Italian gut microbiota. At the phylum level, Hadza gut microbiota are largely enriched in Proteobacteria and Spirochaetes, which are extremely rare in the Italian gut microbiota, whereas Actinobacteria, an important subdominant component of the Italian gut microbiota, are almost absent. At the genus level, Hadza gut microbiota are comparatively enriched in Prevotella, Eubacterium, Oscillibacter, Butyricicoccus, Sporobacter, Succinivibrio, and Treponema and correspondingly depleted in Bifidobacterium, Bacteroides, Blautia, Dorea, unclassified Lachnospiraceae, Roseburia, Faecalibacterium, Ruminococcus, and unclassified Erysipelotrichaceae. These two studies showed that African gut microbiota have clearly an enterotype Prevotella (enterotype II); the African diet rich in millet/sorghum + local vegetables containing very few lipids and animal proteins allows a mucine degradation in synergy with Desulfovibrionaceae. European gut microbiota (Western diet) have principally an enterotype Bacteroides (enterotype I): the European diet rich in lipids and animal proteins allows energy production from carbohydrates and proteins through fermentation [13]. David et al. [59] compared plant-based diet microbiome (high fibers and low fats and proteins) with animal-based diet microbiome (low fibers and high fats and proteins) and respective changes in microbiome on either diet and demonstrated that a shift toward an animal-based diet increases the abundance of bile-tolerant microorganisms ( Alistipes, Bilophila, and Bacteroides) and decreases the levels of Firmicutes that metabolize dietary plant polysaccharides ( Roseburia, Eubacterium rectale, and Ruminococcus bromii). Moreover, microbial activity trades off between carbohydrate and protein fermentation when the type of diet respectively changes. This change occurred only one day after the diet reached the distal gut microbiota. David et al. [59] showed that diet alters human microbiota rapidly and reproducibly” | concepts[109] |
| concept | bile-tolerant microorganisms — not defined in this paper's own words; taxa increased by animal-based diet — “While the microbiome of a healthy individual is relatively stable, gut microbial dynamics can certainly be influenced by lifestyle and dietary cultural choices [56]. A study of European children (fed with the Western diet) and Burkina Faso children (assuming a diet rich in millet/sorghum + local vegetables containing very few lipids and animal proteins) [57] revealed that African children’s microbiota have a remarkable abundance of Prevotella and Xylanibacter. Furthermore, Shigella and Escherichia are widely under-represented. Another study [58] compared Hadza hunter-gatherers and Italian gut microbiota. At the phylum level, Hadza gut microbiota are largely enriched in Proteobacteria and Spirochaetes, which are extremely rare in the Italian gut microbiota, whereas Actinobacteria, an important subdominant component of the Italian gut microbiota, are almost absent. At the genus level, Hadza gut microbiota are comparatively enriched in Prevotella, Eubacterium, Oscillibacter, Butyricicoccus, Sporobacter, Succinivibrio, and Treponema and correspondingly depleted in Bifidobacterium, Bacteroides, Blautia, Dorea, unclassified Lachnospiraceae, Roseburia, Faecalibacterium, Ruminococcus, and unclassified Erysipelotrichaceae. These two studies showed that African gut microbiota have clearly an enterotype Prevotella (enterotype II); the African diet rich in millet/sorghum + local vegetables containing very few lipids and animal proteins allows a mucine degradation in synergy with Desulfovibrionaceae. European gut microbiota (Western diet) have principally an enterotype Bacteroides (enterotype I): the European diet rich in lipids and animal proteins allows energy production from carbohydrates and proteins through fermentation [13]. David et al. [59] compared plant-based diet microbiome (high fibers and low fats and proteins) with animal-based diet microbiome (low fibers and high fats and proteins) and respective changes in microbiome on either diet and demonstrated that a shift toward an animal-based diet increases the abundance of bile-tolerant microorganisms ( Alistipes, Bilophila, and Bacteroides) and decreases the levels of Firmicutes that metabolize dietary plant polysaccharides ( Roseburia, Eubacterium rectale, and Ruminococcus bromii). Moreover, microbial activity trades off between carbohydrate and protein fermentation when the type of diet respectively changes. This change occurred only one day after the diet reached the distal gut microbiota. David et al. [59] showed that diet alters human microbiota rapidly and reproducibly” | concepts[110] |
| concept | carbohydrate and protein fermentation — not defined in this paper's own words; microbial activity shifting with diet — “While the microbiome of a healthy individual is relatively stable, gut microbial dynamics can certainly be influenced by lifestyle and dietary cultural choices [56]. A study of European children (fed with the Western diet) and Burkina Faso children (assuming a diet rich in millet/sorghum + local vegetables containing very few lipids and animal proteins) [57] revealed that African children’s microbiota have a remarkable abundance of Prevotella and Xylanibacter. Furthermore, Shigella and Escherichia are widely under-represented. Another study [58] compared Hadza hunter-gatherers and Italian gut microbiota. At the phylum level, Hadza gut microbiota are largely enriched in Proteobacteria and Spirochaetes, which are extremely rare in the Italian gut microbiota, whereas Actinobacteria, an important subdominant component of the Italian gut microbiota, are almost absent. At the genus level, Hadza gut microbiota are comparatively enriched in Prevotella, Eubacterium, Oscillibacter, Butyricicoccus, Sporobacter, Succinivibrio, and Treponema and correspondingly depleted in Bifidobacterium, Bacteroides, Blautia, Dorea, unclassified Lachnospiraceae, Roseburia, Faecalibacterium, Ruminococcus, and unclassified Erysipelotrichaceae. These two studies showed that African gut microbiota have clearly an enterotype Prevotella (enterotype II); the African diet rich in millet/sorghum + local vegetables containing very few lipids and animal proteins allows a mucine degradation in synergy with Desulfovibrionaceae. European gut microbiota (Western diet) have principally an enterotype Bacteroides (enterotype I): the European diet rich in lipids and animal proteins allows energy production from carbohydrates and proteins through fermentation [13]. David et al. [59] compared plant-based diet microbiome (high fibers and low fats and proteins) with animal-based diet microbiome (low fibers and high fats and proteins) and respective changes in microbiome on either diet and demonstrated that a shift toward an animal-based diet increases the abundance of bile-tolerant microorganisms ( Alistipes, Bilophila, and Bacteroides) and decreases the levels of Firmicutes that metabolize dietary plant polysaccharides ( Roseburia, Eubacterium rectale, and Ruminococcus bromii). Moreover, microbial activity trades off between carbohydrate and protein fermentation when the type of diet respectively changes. This change occurred only one day after the diet reached the distal gut microbiota. David et al. [59] showed that diet alters human microbiota rapidly and reproducibly” | concepts[111] |
| concept | Daily exercise — not defined in this paper's own words; activity exposure increasing microbial diversity — “suggested associations of exercise frequency with gut microbiota composition of young children and adolescents. Daily exercise increases gut microbial diversity ( Table 2) with a Firmicutes enrichment microbiota: Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae by producing more SCFAs which may increase the expression of tight junction proteins in colon epithelia to heighten the resistance of the intestinal barrier, reduce mucosal permeability, and inhibit inflammatory cytokines [50, 60]. Clarke et al. [61] explored exercise and protein consumption for their impact on the gut microbiota of professional athletes from an international rugby union squad. A higher alpha diversity of gut microorganisms representing more than 20 distinct phyla has been demonstrated in athletes compared with high and low BMI controls [61]. Indeed, this study showed that exercise increases gut microbial diversity ( Table 2) and protein consumption positively correlates with microbial diversity. These results provide evidence for a beneficial impact of exercise on gut microbiota diversity, but also indicate that the relationship exercise–microbiota diversity is probably related to accompanying dietary extremes” | concepts[112] |
| concept | tight junction proteins — not defined in this paper's own words; barrier proteins potentially increased by SCFAs — “suggested associations of exercise frequency with gut microbiota composition of young children and adolescents. Daily exercise increases gut microbial diversity ( Table 2) with a Firmicutes enrichment microbiota: Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae by producing more SCFAs which may increase the expression of tight junction proteins in colon epithelia to heighten the resistance of the intestinal barrier, reduce mucosal permeability, and inhibit inflammatory cytokines [50, 60]. Clarke et al. [61] explored exercise and protein consumption for their impact on the gut microbiota of professional athletes from an international rugby union squad. A higher alpha diversity of gut microorganisms representing more than 20 distinct phyla has been demonstrated in athletes compared with high and low BMI controls [61]. Indeed, this study showed that exercise increases gut microbial diversity ( Table 2) and protein consumption positively correlates with microbial diversity. These results provide evidence for a beneficial impact of exercise on gut microbiota diversity, but also indicate that the relationship exercise–microbiota diversity is probably related to accompanying dietary extremes” | concepts[113] |
| concept | mucosal permeability — not defined in this paper's own words; barrier leakiness potentially reduced by exercise-linked SCFAs — “suggested associations of exercise frequency with gut microbiota composition of young children and adolescents. Daily exercise increases gut microbial diversity ( Table 2) with a Firmicutes enrichment microbiota: Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae by producing more SCFAs which may increase the expression of tight junction proteins in colon epithelia to heighten the resistance of the intestinal barrier, reduce mucosal permeability, and inhibit inflammatory cytokines [50, 60]. Clarke et al. [61] explored exercise and protein consumption for their impact on the gut microbiota of professional athletes from an international rugby union squad. A higher alpha diversity of gut microorganisms representing more than 20 distinct phyla has been demonstrated in athletes compared with high and low BMI controls [61]. Indeed, this study showed that exercise increases gut microbial diversity ( Table 2) and protein consumption positively correlates with microbial diversity. These results provide evidence for a beneficial impact of exercise on gut microbiota diversity, but also indicate that the relationship exercise–microbiota diversity is probably related to accompanying dietary extremes” | concepts[114] |
| concept | inflammatory cytokines — not defined in this paper's own words; immune mediators potentially inhibited by SCFAs — “suggested associations of exercise frequency with gut microbiota composition of young children and adolescents. Daily exercise increases gut microbial diversity ( Table 2) with a Firmicutes enrichment microbiota: Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae by producing more SCFAs which may increase the expression of tight junction proteins in colon epithelia to heighten the resistance of the intestinal barrier, reduce mucosal permeability, and inhibit inflammatory cytokines [50, 60]. Clarke et al. [61] explored exercise and protein consumption for their impact on the gut microbiota of professional athletes from an international rugby union squad. A higher alpha diversity of gut microorganisms representing more than 20 distinct phyla has been demonstrated in athletes compared with high and low BMI controls [61]. Indeed, this study showed that exercise increases gut microbial diversity ( Table 2) and protein consumption positively correlates with microbial diversity. These results provide evidence for a beneficial impact of exercise on gut microbiota diversity, but also indicate that the relationship exercise–microbiota diversity is probably related to accompanying dietary extremes” | concepts[115] |
| concept | physiological gut microbiota variations — not defined in this paper's own words; healthy variation across age, ethnicity, lifestyle, and diet — “Gut microbiota composition is highly variable. The variation itself is considered as physiological in the context of healthy gut microbiota, according to age, ethnicity, lifestyle, and dietary habits. However, these physiological gut microbiota variations have huge implications in intestinal and extra-intestinal disorders. Indeed, dysbiosis is often defined as an alteration of gut microbiota composition and a cause or a consequence of disorders. It is often difficult to ascertain whether the change is beneficial or detrimental. As for the human conditions, changes represent a challenge for a better adaptation in a new context and may potentiate resilience. However, a chronic external stimulation may be stressful and disruptive for an unstructured ecosystem. We will discuss the correlations between several diseases and alterations of gut microbiota composition” | concepts[116] |
| concept | alteration of gut microbiota composition — not defined in this paper's own words; paper's definition of dysbiosis — “Gut microbiota composition is highly variable. The variation itself is considered as physiological in the context of healthy gut microbiota, according to age, ethnicity, lifestyle, and dietary habits. However, these physiological gut microbiota variations have huge implications in intestinal and extra-intestinal disorders. Indeed, dysbiosis is often defined as an alteration of gut microbiota composition and a cause or a consequence of disorders. It is often difficult to ascertain whether the change is beneficial or detrimental. As for the human conditions, changes represent a challenge for a better adaptation in a new context and may potentiate resilience. However, a chronic external stimulation may be stressful and disruptive for an unstructured ecosystem. We will discuss the correlations between several diseases and alterations of gut microbiota composition” | concepts[117] |
| concept | chronic external stimulation — not defined in this paper's own words; stressful perturbation of an unstructured ecosystem — “Gut microbiota composition is highly variable. The variation itself is considered as physiological in the context of healthy gut microbiota, according to age, ethnicity, lifestyle, and dietary habits. However, these physiological gut microbiota variations have huge implications in intestinal and extra-intestinal disorders. Indeed, dysbiosis is often defined as an alteration of gut microbiota composition and a cause or a consequence of disorders. It is often difficult to ascertain whether the change is beneficial or detrimental. As for the human conditions, changes represent a challenge for a better adaptation in a new context and may potentiate resilience. However, a chronic external stimulation may be stressful and disruptive for an unstructured ecosystem. We will discuss the correlations between several diseases and alterations of gut microbiota composition” | concepts[118] |
| concept | unstructured ecosystem — not defined in this paper's own words; community state vulnerable to chronic stimulation — “Gut microbiota composition is highly variable. The variation itself is considered as physiological in the context of healthy gut microbiota, according to age, ethnicity, lifestyle, and dietary habits. However, these physiological gut microbiota variations have huge implications in intestinal and extra-intestinal disorders. Indeed, dysbiosis is often defined as an alteration of gut microbiota composition and a cause or a consequence of disorders. It is often difficult to ascertain whether the change is beneficial or detrimental. As for the human conditions, changes represent a challenge for a better adaptation in a new context and may potentiate resilience. However, a chronic external stimulation may be stressful and disruptive for an unstructured ecosystem. We will discuss the correlations between several diseases and alterations of gut microbiota composition” | concepts[119] |
| concept | irritable bowel syndrome (IBS) — not defined in this paper's own words; common GI disorder associated with richness loss — “Irritable bowel syndrome (IBS) is one of the most common gastrointestinal (GI) disorders and the bacterial role has been largely investigated [62]. The study [63] of fecal and colonic mucosal biopsy samples from IBS patients and healthy controls demonstrated a significant reduction in the concentration of aerobic bacteria such as the Lactobacillus species in fecal samples from IBS patients compared to healthy controls. Another study [64] demonstrated that the microbial communities of IBS patients are enriched in Proteobacteria and Firmicutes but reduced in Actinobacteria and Bacteroidetes compared to controls. In particular, 16S rDNA sequences belonging to the family Lachnospiraceae within the phylum Firmicutes are in greater abundance in the IBS clone library [64]. Other studies [62, 65] confirmed and revealed some phyla and genera variations in IBS patients compared to healthy controls: an increase in the Firmicutes-to Bacteroidetes-ratio, a decrease in some Firmicutes families ( Lactobacilli, Faecalibacterium) and the Actinobacteria population (Bifidobacteria, Collinsella), and an increase in some Firmicutes families ( Veillonella, Streptococci, and Ruminococcus spp.) and in Proteobacteria ( Enterobacteriaceae spp.). Therefore, these findings demonstrated a loss of microbial richness that may be involved in amino acid synthesis, in the integrity of cellular junctions, and in inflammatory response, suggesting a weakness of the epithelial barrier functions partially explaining IBS symptoms” | concepts[120] |
| concept | loss of microbial richness — not defined in this paper's own words; IBS-associated loss linked to barrier and inflammatory functions — “Irritable bowel syndrome (IBS) is one of the most common gastrointestinal (GI) disorders and the bacterial role has been largely investigated [62]. The study [63] of fecal and colonic mucosal biopsy samples from IBS patients and healthy controls demonstrated a significant reduction in the concentration of aerobic bacteria such as the Lactobacillus species in fecal samples from IBS patients compared to healthy controls. Another study [64] demonstrated that the microbial communities of IBS patients are enriched in Proteobacteria and Firmicutes but reduced in Actinobacteria and Bacteroidetes compared to controls. In particular, 16S rDNA sequences belonging to the family Lachnospiraceae within the phylum Firmicutes are in greater abundance in the IBS clone library [64]. Other studies [62, 65] confirmed and revealed some phyla and genera variations in IBS patients compared to healthy controls: an increase in the Firmicutes-to Bacteroidetes-ratio, a decrease in some Firmicutes families ( Lactobacilli, Faecalibacterium) and the Actinobacteria population (Bifidobacteria, Collinsella), and an increase in some Firmicutes families ( Veillonella, Streptococci, and Ruminococcus spp.) and in Proteobacteria ( Enterobacteriaceae spp.). Therefore, these findings demonstrated a loss of microbial richness that may be involved in amino acid synthesis, in the integrity of cellular junctions, and in inflammatory response, suggesting a weakness of the epithelial barrier functions partially explaining IBS symptoms” | concepts[121] |
| concept | epithelial barrier functions — not defined in this paper's own words; functions weakened in the paper's IBS account — “Irritable bowel syndrome (IBS) is one of the most common gastrointestinal (GI) disorders and the bacterial role has been largely investigated [62]. The study [63] of fecal and colonic mucosal biopsy samples from IBS patients and healthy controls demonstrated a significant reduction in the concentration of aerobic bacteria such as the Lactobacillus species in fecal samples from IBS patients compared to healthy controls. Another study [64] demonstrated that the microbial communities of IBS patients are enriched in Proteobacteria and Firmicutes but reduced in Actinobacteria and Bacteroidetes compared to controls. In particular, 16S rDNA sequences belonging to the family Lachnospiraceae within the phylum Firmicutes are in greater abundance in the IBS clone library [64]. Other studies [62, 65] confirmed and revealed some phyla and genera variations in IBS patients compared to healthy controls: an increase in the Firmicutes-to Bacteroidetes-ratio, a decrease in some Firmicutes families ( Lactobacilli, Faecalibacterium) and the Actinobacteria population (Bifidobacteria, Collinsella), and an increase in some Firmicutes families ( Veillonella, Streptococci, and Ruminococcus spp.) and in Proteobacteria ( Enterobacteriaceae spp.). Therefore, these findings demonstrated a loss of microbial richness that may be involved in amino acid synthesis, in the integrity of cellular junctions, and in inflammatory response, suggesting a weakness of the epithelial barrier functions partially explaining IBS symptoms” | concepts[122] |
| concept | inflammatory bowel diseases (IBD) — not defined in this paper's own words; chronic relapsing GI inflammatory conditions — “Inflammatory bowel diseases (IBD) gather idiopathic, chronic, and relapsing inflammatory conditions of the gastrointestinal tract including ulcerative colitis (UC) and Crohn’s disease (CRD). The findings of Frank et al. [66] indicated a diminution of Lachnospiraceae and Bacteroidetes microbial populations and an increase in Proteobacteria families in IBD patients compared to control gut microbiota. Gut microbiota variations appear to be different between UC and CRD. Indeed, a decreased abundance of the butyrate-producing bacteria Roseburia hominis and Faecalibacterium prausnitzii has been observed in UC patients relative to controls [67], whereas the opposite has been observed in CRD patients, who are provided with increased Faecalibacterium prausnitzii levels in addition to a reduced overall diversity [68]. In the case of CRD patients, another study [69] demonstrated a decrease in Dialister invisus, an uncharacterized species of Clostridium spp., in Faecalibacterium prausnitzii, and in Bifidobacterium adolescentis and an increase in Ruminococcus gnavus. Sokol et al. [70] confirmed the reduction of F. prausnitzii in CRD patients and also demonstrated that an oral administration of live Faecalibacterium prausnitzii reduced the severity of colitis and tended to correct the dysbiosis. These results suggest that counterbalancing dysbiosis using Faecalibacterium prausnitzii as a probiotic is a promising strategy in CRD treatment [70]. These results do not demonstrate a causal relationship between microbial dysbiosis and IBD pathophysiology, but they rather suggest that gut microbial unbalances are likely to contribute to disease severity” | concepts[123] |
| concept | ulcerative colitis (UC) — not defined in this paper's own words; IBD condition contrasted with Crohn's disease — “Inflammatory bowel diseases (IBD) gather idiopathic, chronic, and relapsing inflammatory conditions of the gastrointestinal tract including ulcerative colitis (UC) and Crohn’s disease (CRD). The findings of Frank et al. [66] indicated a diminution of Lachnospiraceae and Bacteroidetes microbial populations and an increase in Proteobacteria families in IBD patients compared to control gut microbiota. Gut microbiota variations appear to be different between UC and CRD. Indeed, a decreased abundance of the butyrate-producing bacteria Roseburia hominis and Faecalibacterium prausnitzii has been observed in UC patients relative to controls [67], whereas the opposite has been observed in CRD patients, who are provided with increased Faecalibacterium prausnitzii levels in addition to a reduced overall diversity [68]. In the case of CRD patients, another study [69] demonstrated a decrease in Dialister invisus, an uncharacterized species of Clostridium spp., in Faecalibacterium prausnitzii, and in Bifidobacterium adolescentis and an increase in Ruminococcus gnavus. Sokol et al. [70] confirmed the reduction of F. prausnitzii in CRD patients and also demonstrated that an oral administration of live Faecalibacterium prausnitzii reduced the severity of colitis and tended to correct the dysbiosis. These results suggest that counterbalancing dysbiosis using Faecalibacterium prausnitzii as a probiotic is a promising strategy in CRD treatment [70]. These results do not demonstrate a causal relationship between microbial dysbiosis and IBD pathophysiology, but they rather suggest that gut microbial unbalances are likely to contribute to disease severity” | concepts[124] |
| concept | Crohn’s disease (CRD) — not defined in this paper's own words; IBD condition with reduced overall diversity — “Inflammatory bowel diseases (IBD) gather idiopathic, chronic, and relapsing inflammatory conditions of the gastrointestinal tract including ulcerative colitis (UC) and Crohn’s disease (CRD). The findings of Frank et al. [66] indicated a diminution of Lachnospiraceae and Bacteroidetes microbial populations and an increase in Proteobacteria families in IBD patients compared to control gut microbiota. Gut microbiota variations appear to be different between UC and CRD. Indeed, a decreased abundance of the butyrate-producing bacteria Roseburia hominis and Faecalibacterium prausnitzii has been observed in UC patients relative to controls [67], whereas the opposite has been observed in CRD patients, who are provided with increased Faecalibacterium prausnitzii levels in addition to a reduced overall diversity [68]. In the case of CRD patients, another study [69] demonstrated a decrease in Dialister invisus, an uncharacterized species of Clostridium spp., in Faecalibacterium prausnitzii, and in Bifidobacterium adolescentis and an increase in Ruminococcus gnavus. Sokol et al. [70] confirmed the reduction of F. prausnitzii in CRD patients and also demonstrated that an oral administration of live Faecalibacterium prausnitzii reduced the severity of colitis and tended to correct the dysbiosis. These results suggest that counterbalancing dysbiosis using Faecalibacterium prausnitzii as a probiotic is a promising strategy in CRD treatment [70]. These results do not demonstrate a causal relationship between microbial dysbiosis and IBD pathophysiology, but they rather suggest that gut microbial unbalances are likely to contribute to disease severity” | concepts[125] |
| concept | butyrate-producing bacteria — not defined in this paper's own words; functional bacterial group altered in IBD and CRC — “Inflammatory bowel diseases (IBD) gather idiopathic, chronic, and relapsing inflammatory conditions of the gastrointestinal tract including ulcerative colitis (UC) and Crohn’s disease (CRD). The findings of Frank et al. [66] indicated a diminution of Lachnospiraceae and Bacteroidetes microbial populations and an increase in Proteobacteria families in IBD patients compared to control gut microbiota. Gut microbiota variations appear to be different between UC and CRD. Indeed, a decreased abundance of the butyrate-producing bacteria Roseburia hominis and Faecalibacterium prausnitzii has been observed in UC patients relative to controls [67], whereas the opposite has been observed in CRD patients, who are provided with increased Faecalibacterium prausnitzii levels in addition to a reduced overall diversity [68]. In the case of CRD patients, another study [69] demonstrated a decrease in Dialister invisus, an uncharacterized species of Clostridium spp., in Faecalibacterium prausnitzii, and in Bifidobacterium adolescentis and an increase in Ruminococcus gnavus. Sokol et al. [70] confirmed the reduction of F. prausnitzii in CRD patients and also demonstrated that an oral administration of live Faecalibacterium prausnitzii reduced the severity of colitis and tended to correct the dysbiosis. These results suggest that counterbalancing dysbiosis using Faecalibacterium prausnitzii as a probiotic is a promising strategy in CRD treatment [70]. These results do not demonstrate a causal relationship between microbial dysbiosis and IBD pathophysiology, but they rather suggest that gut microbial unbalances are likely to contribute to disease severity” | concepts[126] |
| concept | Faecalibacterium prausnitzii — not defined in this paper's own words; bacterium tested as a probiotic in colitis — “Inflammatory bowel diseases (IBD) gather idiopathic, chronic, and relapsing inflammatory conditions of the gastrointestinal tract including ulcerative colitis (UC) and Crohn’s disease (CRD). The findings of Frank et al. [66] indicated a diminution of Lachnospiraceae and Bacteroidetes microbial populations and an increase in Proteobacteria families in IBD patients compared to control gut microbiota. Gut microbiota variations appear to be different between UC and CRD. Indeed, a decreased abundance of the butyrate-producing bacteria Roseburia hominis and Faecalibacterium prausnitzii has been observed in UC patients relative to controls [67], whereas the opposite has been observed in CRD patients, who are provided with increased Faecalibacterium prausnitzii levels in addition to a reduced overall diversity [68]. In the case of CRD patients, another study [69] demonstrated a decrease in Dialister invisus, an uncharacterized species of Clostridium spp., in Faecalibacterium prausnitzii, and in Bifidobacterium adolescentis and an increase in Ruminococcus gnavus. Sokol et al. [70] confirmed the reduction of F. prausnitzii in CRD patients and also demonstrated that an oral administration of live Faecalibacterium prausnitzii reduced the severity of colitis and tended to correct the dysbiosis. These results suggest that counterbalancing dysbiosis using Faecalibacterium prausnitzii as a probiotic is a promising strategy in CRD treatment [70]. These results do not demonstrate a causal relationship between microbial dysbiosis and IBD pathophysiology, but they rather suggest that gut microbial unbalances are likely to contribute to disease severity” | concepts[127] |
| concept | oral administration — not defined in this paper's own words; live-F. prausnitzii probiotic intervention reducing colitis severity — “Inflammatory bowel diseases (IBD) gather idiopathic, chronic, and relapsing inflammatory conditions of the gastrointestinal tract including ulcerative colitis (UC) and Crohn’s disease (CRD). The findings of Frank et al. [66] indicated a diminution of Lachnospiraceae and Bacteroidetes microbial populations and an increase in Proteobacteria families in IBD patients compared to control gut microbiota. Gut microbiota variations appear to be different between UC and CRD. Indeed, a decreased abundance of the butyrate-producing bacteria Roseburia hominis and Faecalibacterium prausnitzii has been observed in UC patients relative to controls [67], whereas the opposite has been observed in CRD patients, who are provided with increased Faecalibacterium prausnitzii levels in addition to a reduced overall diversity [68]. In the case of CRD patients, another study [69] demonstrated a decrease in Dialister invisus, an uncharacterized species of Clostridium spp., in Faecalibacterium prausnitzii, and in Bifidobacterium adolescentis and an increase in Ruminococcus gnavus. Sokol et al. [70] confirmed the reduction of F. prausnitzii in CRD patients and also demonstrated that an oral administration of live Faecalibacterium prausnitzii reduced the severity of colitis and tended to correct the dysbiosis. These results suggest that counterbalancing dysbiosis using Faecalibacterium prausnitzii as a probiotic is a promising strategy in CRD treatment [70]. These results do not demonstrate a causal relationship between microbial dysbiosis and IBD pathophysiology, but they rather suggest that gut microbial unbalances are likely to contribute to disease severity” | concepts[128] |
| concept | severity of colitis — not defined in this paper's own words; outcome reduced in the live-bacterium intervention — “Inflammatory bowel diseases (IBD) gather idiopathic, chronic, and relapsing inflammatory conditions of the gastrointestinal tract including ulcerative colitis (UC) and Crohn’s disease (CRD). The findings of Frank et al. [66] indicated a diminution of Lachnospiraceae and Bacteroidetes microbial populations and an increase in Proteobacteria families in IBD patients compared to control gut microbiota. Gut microbiota variations appear to be different between UC and CRD. Indeed, a decreased abundance of the butyrate-producing bacteria Roseburia hominis and Faecalibacterium prausnitzii has been observed in UC patients relative to controls [67], whereas the opposite has been observed in CRD patients, who are provided with increased Faecalibacterium prausnitzii levels in addition to a reduced overall diversity [68]. In the case of CRD patients, another study [69] demonstrated a decrease in Dialister invisus, an uncharacterized species of Clostridium spp., in Faecalibacterium prausnitzii, and in Bifidobacterium adolescentis and an increase in Ruminococcus gnavus. Sokol et al. [70] confirmed the reduction of F. prausnitzii in CRD patients and also demonstrated that an oral administration of live Faecalibacterium prausnitzii reduced the severity of colitis and tended to correct the dysbiosis. These results suggest that counterbalancing dysbiosis using Faecalibacterium prausnitzii as a probiotic is a promising strategy in CRD treatment [70]. These results do not demonstrate a causal relationship between microbial dysbiosis and IBD pathophysiology, but they rather suggest that gut microbial unbalances are likely to contribute to disease severity” | concepts[129] |
| concept | celiac disease (CD) — not defined in this paper's own words; gluten-triggered inflammatory intestinal disorder — “Celiac disease (CD) is a chronic intestinal inflammatory disorder due to an aberrant immune response to dietary gluten proteins in genetically predisposed individuals. Gut microbiota variations may play a significant role in the pathogenesis of CD; indeed, dysbiosis is linked with an inflammatory milieu in celiac patients [71]. Celiac disease is caused by the interplay between gluten, genetic factors, and environmental factors such as gut microbiota [72]. Studies [73, 74, 75, 76] have demonstrated that Bifidobacterium spp., Bifidobacterium longum, Clostridium histolyticum, C. lituseburense, and Faecalibacterium prausnitzii group proportions are less abundant in untreated CD patients than in healthy controls. Indeed, patients with CD show a reduction in beneficial species ( Lactobacillus and Bifidobacterium) and an increase in those potentially pathogenic ( Bacteroides and E. coli) as compared to healthy subjects [74]. The mucosal layer of CD patients fails to stabilize the gut microbiota and fails to prevent the host from the invasion of harmful antigens and pathogens [71]. This dysbiosis is reduced, but may still remain, after a gluten-free diet” | concepts[130] |
| concept | interplay between gluten, genetic factors, and environmental factors — not defined in this paper's own words; multifactorial cause assigned to celiac disease — “Celiac disease (CD) is a chronic intestinal inflammatory disorder due to an aberrant immune response to dietary gluten proteins in genetically predisposed individuals. Gut microbiota variations may play a significant role in the pathogenesis of CD; indeed, dysbiosis is linked with an inflammatory milieu in celiac patients [71]. Celiac disease is caused by the interplay between gluten, genetic factors, and environmental factors such as gut microbiota [72]. Studies [73, 74, 75, 76] have demonstrated that Bifidobacterium spp., Bifidobacterium longum, Clostridium histolyticum, C. lituseburense, and Faecalibacterium prausnitzii group proportions are less abundant in untreated CD patients than in healthy controls. Indeed, patients with CD show a reduction in beneficial species ( Lactobacillus and Bifidobacterium) and an increase in those potentially pathogenic ( Bacteroides and E. coli) as compared to healthy subjects [74]. The mucosal layer of CD patients fails to stabilize the gut microbiota and fails to prevent the host from the invasion of harmful antigens and pathogens [71]. This dysbiosis is reduced, but may still remain, after a gluten-free diet” | concepts[131] |
| concept | gluten-free diet — not defined in this paper's own words; dietary treatment reducing but not always eliminating dysbiosis — “Celiac disease (CD) is a chronic intestinal inflammatory disorder due to an aberrant immune response to dietary gluten proteins in genetically predisposed individuals. Gut microbiota variations may play a significant role in the pathogenesis of CD; indeed, dysbiosis is linked with an inflammatory milieu in celiac patients [71]. Celiac disease is caused by the interplay between gluten, genetic factors, and environmental factors such as gut microbiota [72]. Studies [73, 74, 75, 76] have demonstrated that Bifidobacterium spp., Bifidobacterium longum, Clostridium histolyticum, C. lituseburense, and Faecalibacterium prausnitzii group proportions are less abundant in untreated CD patients than in healthy controls. Indeed, patients with CD show a reduction in beneficial species ( Lactobacillus and Bifidobacterium) and an increase in those potentially pathogenic ( Bacteroides and E. coli) as compared to healthy subjects [74]. The mucosal layer of CD patients fails to stabilize the gut microbiota and fails to prevent the host from the invasion of harmful antigens and pathogens [71]. This dysbiosis is reduced, but may still remain, after a gluten-free diet” | concepts[132] |
| concept | colorectal cancer — not defined in this paper's own words; cancer associated with structural microbiota imbalance — “Colorectal cancer is the third most common cause of cancer mortality in the world [77]. Structural fecal bacterial segregations between CRC patients and healthy volunteers have been demonstrated [78]. The gut microbiota of the CRC patients were enriched in Bacteroides fragilis, Enterococcus, Escherichia/Shigella, Klebsiella, Streptococcus, and Peptostreptococcus and were impoverished in Roseburia and other butyrate-producing bacteria of the family Lachnospiraceae [78]. The gut microbiota of the healthy volunteers were enriched in Bacteroides vulgatus and Bacteroides uniformis. Therefore, gut microbiota variations, such as a reduction of butyrate producers and an increase in opportunistic pathogens, constitute a major structural imbalance of gut microbiota in CRC patients. Shen et al. [79] demonstrated a higher abundance of Proteobacteria and a lower abundance of Bacteroidetes in CRC cases compared to controls. At the genus level, CRC cases showed an increased abundance of Dorea spp. and Faecalibacterium spp. and lower proportions of Bacteroides spp. and Coprococcus spp. than controls. Genomic analysis identified an association of Fusobacterium spp. with colorectal cancer [80]; the microbiota of CRC patients were enriched in Fusobacterium spp., whereas the Bacteroidetes and Firmicutes phyla were depleted. Furthermore, Fusobacterium spp. may contribute to tumorigenesis by an inflammatory-mediated mechanism [80], but the precise role of Fusobacteria in colorectal carcinoma pathogenesis requires further investigation. All these findings reveal alterations in CRC microbiota that may contribute to the etiology of colorectal cancer. The extension of these findings may lead to strategies able to manipulate microbiota to prevent colorectal cancer as well as to identify individuals at high risk” | concepts[133] |
| concept | opportunistic pathogens — not defined in this paper's own words; taxa increased in colorectal-cancer microbiota — “Colorectal cancer is the third most common cause of cancer mortality in the world [77]. Structural fecal bacterial segregations between CRC patients and healthy volunteers have been demonstrated [78]. The gut microbiota of the CRC patients were enriched in Bacteroides fragilis, Enterococcus, Escherichia/Shigella, Klebsiella, Streptococcus, and Peptostreptococcus and were impoverished in Roseburia and other butyrate-producing bacteria of the family Lachnospiraceae [78]. The gut microbiota of the healthy volunteers were enriched in Bacteroides vulgatus and Bacteroides uniformis. Therefore, gut microbiota variations, such as a reduction of butyrate producers and an increase in opportunistic pathogens, constitute a major structural imbalance of gut microbiota in CRC patients. Shen et al. [79] demonstrated a higher abundance of Proteobacteria and a lower abundance of Bacteroidetes in CRC cases compared to controls. At the genus level, CRC cases showed an increased abundance of Dorea spp. and Faecalibacterium spp. and lower proportions of Bacteroides spp. and Coprococcus spp. than controls. Genomic analysis identified an association of Fusobacterium spp. with colorectal cancer [80]; the microbiota of CRC patients were enriched in Fusobacterium spp., whereas the Bacteroidetes and Firmicutes phyla were depleted. Furthermore, Fusobacterium spp. may contribute to tumorigenesis by an inflammatory-mediated mechanism [80], but the precise role of Fusobacteria in colorectal carcinoma pathogenesis requires further investigation. All these findings reveal alterations in CRC microbiota that may contribute to the etiology of colorectal cancer. The extension of these findings may lead to strategies able to manipulate microbiota to prevent colorectal cancer as well as to identify individuals at high risk” | concepts[134] |
| concept | Fusobacterium — not defined in this paper's own words; taxon associated with colorectal cancer — “Colorectal cancer is the third most common cause of cancer mortality in the world [77]. Structural fecal bacterial segregations between CRC patients and healthy volunteers have been demonstrated [78]. The gut microbiota of the CRC patients were enriched in Bacteroides fragilis, Enterococcus, Escherichia/Shigella, Klebsiella, Streptococcus, and Peptostreptococcus and were impoverished in Roseburia and other butyrate-producing bacteria of the family Lachnospiraceae [78]. The gut microbiota of the healthy volunteers were enriched in Bacteroides vulgatus and Bacteroides uniformis. Therefore, gut microbiota variations, such as a reduction of butyrate producers and an increase in opportunistic pathogens, constitute a major structural imbalance of gut microbiota in CRC patients. Shen et al. [79] demonstrated a higher abundance of Proteobacteria and a lower abundance of Bacteroidetes in CRC cases compared to controls. At the genus level, CRC cases showed an increased abundance of Dorea spp. and Faecalibacterium spp. and lower proportions of Bacteroides spp. and Coprococcus spp. than controls. Genomic analysis identified an association of Fusobacterium spp. with colorectal cancer [80]; the microbiota of CRC patients were enriched in Fusobacterium spp., whereas the Bacteroidetes and Firmicutes phyla were depleted. Furthermore, Fusobacterium spp. may contribute to tumorigenesis by an inflammatory-mediated mechanism [80], but the precise role of Fusobacteria in colorectal carcinoma pathogenesis requires further investigation. All these findings reveal alterations in CRC microbiota that may contribute to the etiology of colorectal cancer. The extension of these findings may lead to strategies able to manipulate microbiota to prevent colorectal cancer as well as to identify individuals at high risk” | concepts[135] |
| concept | inflammatory-mediated mechanism — not defined in this paper's own words; possible Fusobacterium contribution to tumorigenesis — “Colorectal cancer is the third most common cause of cancer mortality in the world [77]. Structural fecal bacterial segregations between CRC patients and healthy volunteers have been demonstrated [78]. The gut microbiota of the CRC patients were enriched in Bacteroides fragilis, Enterococcus, Escherichia/Shigella, Klebsiella, Streptococcus, and Peptostreptococcus and were impoverished in Roseburia and other butyrate-producing bacteria of the family Lachnospiraceae [78]. The gut microbiota of the healthy volunteers were enriched in Bacteroides vulgatus and Bacteroides uniformis. Therefore, gut microbiota variations, such as a reduction of butyrate producers and an increase in opportunistic pathogens, constitute a major structural imbalance of gut microbiota in CRC patients. Shen et al. [79] demonstrated a higher abundance of Proteobacteria and a lower abundance of Bacteroidetes in CRC cases compared to controls. At the genus level, CRC cases showed an increased abundance of Dorea spp. and Faecalibacterium spp. and lower proportions of Bacteroides spp. and Coprococcus spp. than controls. Genomic analysis identified an association of Fusobacterium spp. with colorectal cancer [80]; the microbiota of CRC patients were enriched in Fusobacterium spp., whereas the Bacteroidetes and Firmicutes phyla were depleted. Furthermore, Fusobacterium spp. may contribute to tumorigenesis by an inflammatory-mediated mechanism [80], but the precise role of Fusobacteria in colorectal carcinoma pathogenesis requires further investigation. All these findings reveal alterations in CRC microbiota that may contribute to the etiology of colorectal cancer. The extension of these findings may lead to strategies able to manipulate microbiota to prevent colorectal cancer as well as to identify individuals at high risk” | concepts[136] |
| concept | gut–brain axis — not defined in this paper's own words; bidirectional gut-central nervous system interaction — “We highlighted that the pivotal relationship between gut microbiota and the host is involved in many intestinal disorders. Recent advances in research have demonstrated that this mutualistic gut microbiota–host relationship appears to play a critical role for many extra-intestinal diseases such as metabolic diseases and neurological disorders with “gut–brain axis” interactions [81], but also for complex multifactorial diseases such as age-related macular degeneration with “gut–retina axis” interactions” | concepts[137] |
| concept | gut–retina axis — not defined in this paper's own words; gut-linked interaction proposed in macular degeneration — “We highlighted that the pivotal relationship between gut microbiota and the host is involved in many intestinal disorders. Recent advances in research have demonstrated that this mutualistic gut microbiota–host relationship appears to play a critical role for many extra-intestinal diseases such as metabolic diseases and neurological disorders with “gut–brain axis” interactions [81], but also for complex multifactorial diseases such as age-related macular degeneration with “gut–retina axis” interactions” | concepts[138] |
| concept | energy from the diet — not defined in this paper's own words; resource harvested more efficiently by obesity-linked microbiota — “Animal studies constitute the majority of causative evidence linking changes in microbial composition to obesity while, in humans, data are more variable. In addition, although the majority of mouse gut species are unique, the mouse and human microbiota are similar at the division level, with Firmicutes and Bacteroidetes dominating [83]. The analysis [83] of gut microbiota of genetically obese ob/ob mice and lean mice all fed the same polysaccharide-rich diet revealed a lower relative abundance (50%) of Bacteroidetes in obese ob/ob mice, whereas the Firmicutes are correspondingly higher. Indeed, higher numbers of Ruminococcaceae and Rikenellaceae have been observed in leptin-resistant obese (leptin-promoting satiety) and diabetic mice (db/db) compared with their lean littermates [84]. In addition, the higher abundance of Ruminococcaceae and Rikenellaceae in mice fed a high-fat diet is not only dependent on the ingested diet but is also closely linked with obesity and type 2 diabetes [85]. Furthermore, the association between Desulfovibrionaceae abundance and obesity and type 2 diabetes has been demonstrated [86, 87]. Other studies [50, 88] confirmed the role of Proteobacteria in obesity by producing pro-inflammatory molecules such as lipopolysaccharides and helping to harvest energy and increase host fat storage [88]. On the contrary, researchers [86, 89] have recently demonstrated that Akkermansia muciniphila, a mucin-degrading bacteria living in the mucus layer [90], decreases in both genetically and diet-induced obese mice. All these studies highlight the finding that obesity is associated with changes in the composition of gut microbiota including lower species diversity and shifts in the abundance of genes involved in metabolism. These gut microbiota variations affect the microbiome which has an increased capacity to harvest energy from the diet and these changes are transmissible [91]. Gut microbiota can be considered as a contributing factor to the pathophysiology of obesity and may have potential therapeutic implications” | concepts[139] |
| concept | host fat storage — not defined in this paper's own words; storage increased by energy-harvesting and inflammatory taxa — “Animal studies constitute the majority of causative evidence linking changes in microbial composition to obesity while, in humans, data are more variable. In addition, although the majority of mouse gut species are unique, the mouse and human microbiota are similar at the division level, with Firmicutes and Bacteroidetes dominating [83]. The analysis [83] of gut microbiota of genetically obese ob/ob mice and lean mice all fed the same polysaccharide-rich diet revealed a lower relative abundance (50%) of Bacteroidetes in obese ob/ob mice, whereas the Firmicutes are correspondingly higher. Indeed, higher numbers of Ruminococcaceae and Rikenellaceae have been observed in leptin-resistant obese (leptin-promoting satiety) and diabetic mice (db/db) compared with their lean littermates [84]. In addition, the higher abundance of Ruminococcaceae and Rikenellaceae in mice fed a high-fat diet is not only dependent on the ingested diet but is also closely linked with obesity and type 2 diabetes [85]. Furthermore, the association between Desulfovibrionaceae abundance and obesity and type 2 diabetes has been demonstrated [86, 87]. Other studies [50, 88] confirmed the role of Proteobacteria in obesity by producing pro-inflammatory molecules such as lipopolysaccharides and helping to harvest energy and increase host fat storage [88]. On the contrary, researchers [86, 89] have recently demonstrated that Akkermansia muciniphila, a mucin-degrading bacteria living in the mucus layer [90], decreases in both genetically and diet-induced obese mice. All these studies highlight the finding that obesity is associated with changes in the composition of gut microbiota including lower species diversity and shifts in the abundance of genes involved in metabolism. These gut microbiota variations affect the microbiome which has an increased capacity to harvest energy from the diet and these changes are transmissible [91]. Gut microbiota can be considered as a contributing factor to the pathophysiology of obesity and may have potential therapeutic implications” | concepts[140] |
| concept | lipopolysaccharides — not defined in this paper's own words; pro-inflammatory molecules produced by Proteobacteria — “Animal studies constitute the majority of causative evidence linking changes in microbial composition to obesity while, in humans, data are more variable. In addition, although the majority of mouse gut species are unique, the mouse and human microbiota are similar at the division level, with Firmicutes and Bacteroidetes dominating [83]. The analysis [83] of gut microbiota of genetically obese ob/ob mice and lean mice all fed the same polysaccharide-rich diet revealed a lower relative abundance (50%) of Bacteroidetes in obese ob/ob mice, whereas the Firmicutes are correspondingly higher. Indeed, higher numbers of Ruminococcaceae and Rikenellaceae have been observed in leptin-resistant obese (leptin-promoting satiety) and diabetic mice (db/db) compared with their lean littermates [84]. In addition, the higher abundance of Ruminococcaceae and Rikenellaceae in mice fed a high-fat diet is not only dependent on the ingested diet but is also closely linked with obesity and type 2 diabetes [85]. Furthermore, the association between Desulfovibrionaceae abundance and obesity and type 2 diabetes has been demonstrated [86, 87]. Other studies [50, 88] confirmed the role of Proteobacteria in obesity by producing pro-inflammatory molecules such as lipopolysaccharides and helping to harvest energy and increase host fat storage [88]. On the contrary, researchers [86, 89] have recently demonstrated that Akkermansia muciniphila, a mucin-degrading bacteria living in the mucus layer [90], decreases in both genetically and diet-induced obese mice. All these studies highlight the finding that obesity is associated with changes in the composition of gut microbiota including lower species diversity and shifts in the abundance of genes involved in metabolism. These gut microbiota variations affect the microbiome which has an increased capacity to harvest energy from the diet and these changes are transmissible [91]. Gut microbiota can be considered as a contributing factor to the pathophysiology of obesity and may have potential therapeutic implications” | concepts[141] |
| concept | Akkermansia muciniphila — not defined in this paper's own words; mucin-degrading bacterium depleted in obese mice — “Animal studies constitute the majority of causative evidence linking changes in microbial composition to obesity while, in humans, data are more variable. In addition, although the majority of mouse gut species are unique, the mouse and human microbiota are similar at the division level, with Firmicutes and Bacteroidetes dominating [83]. The analysis [83] of gut microbiota of genetically obese ob/ob mice and lean mice all fed the same polysaccharide-rich diet revealed a lower relative abundance (50%) of Bacteroidetes in obese ob/ob mice, whereas the Firmicutes are correspondingly higher. Indeed, higher numbers of Ruminococcaceae and Rikenellaceae have been observed in leptin-resistant obese (leptin-promoting satiety) and diabetic mice (db/db) compared with their lean littermates [84]. In addition, the higher abundance of Ruminococcaceae and Rikenellaceae in mice fed a high-fat diet is not only dependent on the ingested diet but is also closely linked with obesity and type 2 diabetes [85]. Furthermore, the association between Desulfovibrionaceae abundance and obesity and type 2 diabetes has been demonstrated [86, 87]. Other studies [50, 88] confirmed the role of Proteobacteria in obesity by producing pro-inflammatory molecules such as lipopolysaccharides and helping to harvest energy and increase host fat storage [88]. On the contrary, researchers [86, 89] have recently demonstrated that Akkermansia muciniphila, a mucin-degrading bacteria living in the mucus layer [90], decreases in both genetically and diet-induced obese mice. All these studies highlight the finding that obesity is associated with changes in the composition of gut microbiota including lower species diversity and shifts in the abundance of genes involved in metabolism. These gut microbiota variations affect the microbiome which has an increased capacity to harvest energy from the diet and these changes are transmissible [91]. Gut microbiota can be considered as a contributing factor to the pathophysiology of obesity and may have potential therapeutic implications” | concepts[142] |
| concept | type 2 diabetes — not defined in this paper's own words; metabolic disease with altered gut microbiota — “demonstrated that gut microbiota composition is altered in patients suffering from T2D, but it is not clear whether these changes are a cause or simply a consequence of the disorder. Larsen et al. [92] showed that the proportions of phyla Firmicutes and Clostridia are significantly reduced in the T2D sufferers compared to the healthy group. Furthermore, the ratios of Bacteroidetes to Firmicutes, the ratios of Bacteroides-Prevotella, and Betaproteobacteria are highly increased in T2D sufferers compared to healthy patients and positively correlated with plasma glucose. A metagenome-wide association study of gut microbiota of T2D Chinese sufferers [94] demonstrated that patients with type 2 diabetes were characterized by a decrease in butyrate-producing bacteria such as Roseburia spp. and an increase in various opportunistic pathogens ( Clostridium spp., Bacteroides caccae) as well as an enrichment of other microbial functions conferring sulfate reduction ( Desulfovibrionaceae spp.). Gut microbiota interact with various host sensing and signaling pathways, leading to a modulation of the endocrine system, immune responses, nervous system activity, and hence, the predisposition to metabolic diseases. Gut microbiota dysbiosis drives and implies new therapeutic strategies for diabetes and related metabolic diseases” | concepts[143] |
| concept | host sensing and signaling pathways — not defined in this paper's own words; pathways through which microbiota modulate host systems — “demonstrated that gut microbiota composition is altered in patients suffering from T2D, but it is not clear whether these changes are a cause or simply a consequence of the disorder. Larsen et al. [92] showed that the proportions of phyla Firmicutes and Clostridia are significantly reduced in the T2D sufferers compared to the healthy group. Furthermore, the ratios of Bacteroidetes to Firmicutes, the ratios of Bacteroides-Prevotella, and Betaproteobacteria are highly increased in T2D sufferers compared to healthy patients and positively correlated with plasma glucose. A metagenome-wide association study of gut microbiota of T2D Chinese sufferers [94] demonstrated that patients with type 2 diabetes were characterized by a decrease in butyrate-producing bacteria such as Roseburia spp. and an increase in various opportunistic pathogens ( Clostridium spp., Bacteroides caccae) as well as an enrichment of other microbial functions conferring sulfate reduction ( Desulfovibrionaceae spp.). Gut microbiota interact with various host sensing and signaling pathways, leading to a modulation of the endocrine system, immune responses, nervous system activity, and hence, the predisposition to metabolic diseases. Gut microbiota dysbiosis drives and implies new therapeutic strategies for diabetes and related metabolic diseases” | concepts[144] |
| concept | endocrine system — not defined in this paper's own words; host system modulated by microbiota interactions — “demonstrated that gut microbiota composition is altered in patients suffering from T2D, but it is not clear whether these changes are a cause or simply a consequence of the disorder. Larsen et al. [92] showed that the proportions of phyla Firmicutes and Clostridia are significantly reduced in the T2D sufferers compared to the healthy group. Furthermore, the ratios of Bacteroidetes to Firmicutes, the ratios of Bacteroides-Prevotella, and Betaproteobacteria are highly increased in T2D sufferers compared to healthy patients and positively correlated with plasma glucose. A metagenome-wide association study of gut microbiota of T2D Chinese sufferers [94] demonstrated that patients with type 2 diabetes were characterized by a decrease in butyrate-producing bacteria such as Roseburia spp. and an increase in various opportunistic pathogens ( Clostridium spp., Bacteroides caccae) as well as an enrichment of other microbial functions conferring sulfate reduction ( Desulfovibrionaceae spp.). Gut microbiota interact with various host sensing and signaling pathways, leading to a modulation of the endocrine system, immune responses, nervous system activity, and hence, the predisposition to metabolic diseases. Gut microbiota dysbiosis drives and implies new therapeutic strategies for diabetes and related metabolic diseases” | concepts[145] |
| concept | immune responses — not defined in this paper's own words; host responses modulated by microbiota interactions — “demonstrated that gut microbiota composition is altered in patients suffering from T2D, but it is not clear whether these changes are a cause or simply a consequence of the disorder. Larsen et al. [92] showed that the proportions of phyla Firmicutes and Clostridia are significantly reduced in the T2D sufferers compared to the healthy group. Furthermore, the ratios of Bacteroidetes to Firmicutes, the ratios of Bacteroides-Prevotella, and Betaproteobacteria are highly increased in T2D sufferers compared to healthy patients and positively correlated with plasma glucose. A metagenome-wide association study of gut microbiota of T2D Chinese sufferers [94] demonstrated that patients with type 2 diabetes were characterized by a decrease in butyrate-producing bacteria such as Roseburia spp. and an increase in various opportunistic pathogens ( Clostridium spp., Bacteroides caccae) as well as an enrichment of other microbial functions conferring sulfate reduction ( Desulfovibrionaceae spp.). Gut microbiota interact with various host sensing and signaling pathways, leading to a modulation of the endocrine system, immune responses, nervous system activity, and hence, the predisposition to metabolic diseases. Gut microbiota dysbiosis drives and implies new therapeutic strategies for diabetes and related metabolic diseases” | concepts[146] |
| concept | nervous system activity — not defined in this paper's own words; host activity modulated by microbiota interactions — “demonstrated that gut microbiota composition is altered in patients suffering from T2D, but it is not clear whether these changes are a cause or simply a consequence of the disorder. Larsen et al. [92] showed that the proportions of phyla Firmicutes and Clostridia are significantly reduced in the T2D sufferers compared to the healthy group. Furthermore, the ratios of Bacteroidetes to Firmicutes, the ratios of Bacteroides-Prevotella, and Betaproteobacteria are highly increased in T2D sufferers compared to healthy patients and positively correlated with plasma glucose. A metagenome-wide association study of gut microbiota of T2D Chinese sufferers [94] demonstrated that patients with type 2 diabetes were characterized by a decrease in butyrate-producing bacteria such as Roseburia spp. and an increase in various opportunistic pathogens ( Clostridium spp., Bacteroides caccae) as well as an enrichment of other microbial functions conferring sulfate reduction ( Desulfovibrionaceae spp.). Gut microbiota interact with various host sensing and signaling pathways, leading to a modulation of the endocrine system, immune responses, nervous system activity, and hence, the predisposition to metabolic diseases. Gut microbiota dysbiosis drives and implies new therapeutic strategies for diabetes and related metabolic diseases” | concepts[147] |
| concept | bidirectional interactions — not defined in this paper's own words; two-way brain-gut communication — “The brain and the gut are connected via the gut–brain axis with bidirectional interactions between the central nervous system, the enteric nervous system, and the gastrointestinal tract. These bidirectional interactions enable the brain to influence gastrointestinal functions as well as immune functions” | concepts[148] |
| concept | central nervous system — not defined in this paper's own words; brain-side component of the gut-brain axis — “The brain and the gut are connected via the gut–brain axis with bidirectional interactions between the central nervous system, the enteric nervous system, and the gastrointestinal tract. These bidirectional interactions enable the brain to influence gastrointestinal functions as well as immune functions” | concepts[149] |
| concept | enteric nervous system — not defined in this paper's own words; gut neural component of the gut-brain axis — “The brain and the gut are connected via the gut–brain axis with bidirectional interactions between the central nervous system, the enteric nervous system, and the gastrointestinal tract. These bidirectional interactions enable the brain to influence gastrointestinal functions as well as immune functions” | concepts[150] |
| concept | Alzheimer’s disease (AD) — not defined in this paper's own words; neurodegenerative disease associated with altered diversity — “Today, over 46 million people live with dementia worldwide [96]. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are considered the most common forms of dementia in the elderly. Alzheimer’s disease (AD) is a chronic, rapidly progressive neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-beta peptides. Cattaneo et al. [97] demonstrated that an increase in Escherichia/Shigella abundance and a reduction of E. rectale abundance are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. Vogt et al. [98] compared gut microbiota composition from patients with and without a diagnosis of AD and revealed a lower microbial diversity compositionally distinct from control-age and sex-matched individuals, with a decrease in Firmicutes and Bifidobacterium abundance and an increase in Bacteroidetes abundance in the microbiome of AD participants. The gut microbiota variations are also involved in the pathogenesis of PD. Hopfner et al. [99] suggested, in agreement with most other studies [100, 101, 102], an increase in Lactobacillaceae abundance in Parkinson patients compared to healthy controls. Moreover, none of the differences in alpha diversity has been observed between PD cases and controls, whereas beta diversity has been revealed for three bacterial families ( Lactobacillaceae, Barnesiellaceae, and Enterococcaceae) [99]. PD is associated with changes in gut microbiota and this gut microbiota dysbiosis may be the mechanism of neuroinflammation that leads to PD pathology” | concepts[151] |
| concept | Parkinson’s disease (PD) — not defined in this paper's own words; neurological disease associated with dysbiosis — “Today, over 46 million people live with dementia worldwide [96]. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are considered the most common forms of dementia in the elderly. Alzheimer’s disease (AD) is a chronic, rapidly progressive neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-beta peptides. Cattaneo et al. [97] demonstrated that an increase in Escherichia/Shigella abundance and a reduction of E. rectale abundance are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. Vogt et al. [98] compared gut microbiota composition from patients with and without a diagnosis of AD and revealed a lower microbial diversity compositionally distinct from control-age and sex-matched individuals, with a decrease in Firmicutes and Bifidobacterium abundance and an increase in Bacteroidetes abundance in the microbiome of AD participants. The gut microbiota variations are also involved in the pathogenesis of PD. Hopfner et al. [99] suggested, in agreement with most other studies [100, 101, 102], an increase in Lactobacillaceae abundance in Parkinson patients compared to healthy controls. Moreover, none of the differences in alpha diversity has been observed between PD cases and controls, whereas beta diversity has been revealed for three bacterial families ( Lactobacillaceae, Barnesiellaceae, and Enterococcaceae) [99]. PD is associated with changes in gut microbiota and this gut microbiota dysbiosis may be the mechanism of neuroinflammation that leads to PD pathology” | concepts[152] |
| concept | amyloid-beta peptides — not defined in this paper's own words; cerebral accumulation associated with Alzheimer's disease — “Today, over 46 million people live with dementia worldwide [96]. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are considered the most common forms of dementia in the elderly. Alzheimer’s disease (AD) is a chronic, rapidly progressive neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-beta peptides. Cattaneo et al. [97] demonstrated that an increase in Escherichia/Shigella abundance and a reduction of E. rectale abundance are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. Vogt et al. [98] compared gut microbiota composition from patients with and without a diagnosis of AD and revealed a lower microbial diversity compositionally distinct from control-age and sex-matched individuals, with a decrease in Firmicutes and Bifidobacterium abundance and an increase in Bacteroidetes abundance in the microbiome of AD participants. The gut microbiota variations are also involved in the pathogenesis of PD. Hopfner et al. [99] suggested, in agreement with most other studies [100, 101, 102], an increase in Lactobacillaceae abundance in Parkinson patients compared to healthy controls. Moreover, none of the differences in alpha diversity has been observed between PD cases and controls, whereas beta diversity has been revealed for three bacterial families ( Lactobacillaceae, Barnesiellaceae, and Enterococcaceae) [99]. PD is associated with changes in gut microbiota and this gut microbiota dysbiosis may be the mechanism of neuroinflammation that leads to PD pathology” | concepts[153] |
| concept | neuroinflammation — not defined in this paper's own words; possible microbiota-mediated mechanism leading to PD pathology — “Today, over 46 million people live with dementia worldwide [96]. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are considered the most common forms of dementia in the elderly. Alzheimer’s disease (AD) is a chronic, rapidly progressive neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-beta peptides. Cattaneo et al. [97] demonstrated that an increase in Escherichia/Shigella abundance and a reduction of E. rectale abundance are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. Vogt et al. [98] compared gut microbiota composition from patients with and without a diagnosis of AD and revealed a lower microbial diversity compositionally distinct from control-age and sex-matched individuals, with a decrease in Firmicutes and Bifidobacterium abundance and an increase in Bacteroidetes abundance in the microbiome of AD participants. The gut microbiota variations are also involved in the pathogenesis of PD. Hopfner et al. [99] suggested, in agreement with most other studies [100, 101, 102], an increase in Lactobacillaceae abundance in Parkinson patients compared to healthy controls. Moreover, none of the differences in alpha diversity has been observed between PD cases and controls, whereas beta diversity has been revealed for three bacterial families ( Lactobacillaceae, Barnesiellaceae, and Enterococcaceae) [99]. PD is associated with changes in gut microbiota and this gut microbiota dysbiosis may be the mechanism of neuroinflammation that leads to PD pathology” | concepts[154] |
| concept | PD pathology — not defined in this paper's own words; pathology potentially downstream of neuroinflammation — “Today, over 46 million people live with dementia worldwide [96]. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are considered the most common forms of dementia in the elderly. Alzheimer’s disease (AD) is a chronic, rapidly progressive neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-beta peptides. Cattaneo et al. [97] demonstrated that an increase in Escherichia/Shigella abundance and a reduction of E. rectale abundance are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. Vogt et al. [98] compared gut microbiota composition from patients with and without a diagnosis of AD and revealed a lower microbial diversity compositionally distinct from control-age and sex-matched individuals, with a decrease in Firmicutes and Bifidobacterium abundance and an increase in Bacteroidetes abundance in the microbiome of AD participants. The gut microbiota variations are also involved in the pathogenesis of PD. Hopfner et al. [99] suggested, in agreement with most other studies [100, 101, 102], an increase in Lactobacillaceae abundance in Parkinson patients compared to healthy controls. Moreover, none of the differences in alpha diversity has been observed between PD cases and controls, whereas beta diversity has been revealed for three bacterial families ( Lactobacillaceae, Barnesiellaceae, and Enterococcaceae) [99]. PD is associated with changes in gut microbiota and this gut microbiota dysbiosis may be the mechanism of neuroinflammation that leads to PD pathology” | concepts[155] |
| concept | hepatic encephalopathy (HE) — not defined in this paper's own words; neuropsychiatric complication of cirrhosis — “Hepatic encephalopathy (HE) is a complication of cirrhosis and is defined as a spectrum of neuropsychiatric abnormalities in patients with liver dysfunctions. Bajaj et al. [103] linked the gut microbiota composition with cognition and inflammation in HE. Fecal microbiota of cirrhotics were significantly higher in Enterobacteriaceae, Alcaligenaceae, and Fusobacteriaceae and lower in Ruminococcaceae and Lachnospiraceae compared with controls [103]; moreover, altered higher levels of Veillonellaceae were found in HE patients compared with cirrhotics without HE. In the cirrhosis group, Alcaligenaceae and Porphyromonadaceae were positively correlated with cognitive impairment. Fusobacteriaceae, Veillonellaceae, and Enterobacteriaceae were positively and Ruminococcaceae was negatively related to inflammation. Thus, cirrhosis, especially when complicated with HE, is associated with significant gut microbiota alterations compared with healthy individuals. Specific bacterial families ( Alcaligenaceae, Porphyromonadaceae, and Enterobacteriaceae) are strongly associated with cognition and inflammation in HE” | concepts[156] |
| concept | cognitive impairment — not defined in this paper's own words; HE outcome correlated with bacterial families — “Hepatic encephalopathy (HE) is a complication of cirrhosis and is defined as a spectrum of neuropsychiatric abnormalities in patients with liver dysfunctions. Bajaj et al. [103] linked the gut microbiota composition with cognition and inflammation in HE. Fecal microbiota of cirrhotics were significantly higher in Enterobacteriaceae, Alcaligenaceae, and Fusobacteriaceae and lower in Ruminococcaceae and Lachnospiraceae compared with controls [103]; moreover, altered higher levels of Veillonellaceae were found in HE patients compared with cirrhotics without HE. In the cirrhosis group, Alcaligenaceae and Porphyromonadaceae were positively correlated with cognitive impairment. Fusobacteriaceae, Veillonellaceae, and Enterobacteriaceae were positively and Ruminococcaceae was negatively related to inflammation. Thus, cirrhosis, especially when complicated with HE, is associated with significant gut microbiota alterations compared with healthy individuals. Specific bacterial families ( Alcaligenaceae, Porphyromonadaceae, and Enterobacteriaceae) are strongly associated with cognition and inflammation in HE” | concepts[157] |
| concept | autism spectrum disorders — not defined in this paper's own words; conditions with diversity and taxonomic differences — “Autism Spectrum Disorders Compared with the gut microbiota of children without ASD, the gut microbiota of children with ASD is less diverse and exhibits lower levels of Bifidobacterium and Firmicutes and higher levels of Lactobacillus, Clostridium, Bacteroidetes, Desulfovibrio, Caloramator, and Sarcina [104, 105, 106, 107]. A study by Wang et al. [108] showed a decrease in Bifidobacterium spp. and mucolytic bacteria Akkermansia muciniphila in the gut microbiota of autism subjects compared to control subjects. Williams et al. [109] found an increase in the Firmicutes-to-Bacteroidetes ratio and a significant increase in Sutterella compared to their abundance in controls. These findings demonstrated that gut microbiota dysbiosis has close relationships with gastrointestinal and behavioral manifestations of autism” | concepts[158] |
| concept | behavioral manifestations of autism — not defined in this paper's own words; manifestations closely related to dysbiosis — “Compared with the gut microbiota of children without ASD, the gut microbiota of children with ASD is less diverse and exhibits lower levels of Bifidobacterium and Firmicutes and higher levels of Lactobacillus, Clostridium, Bacteroidetes, Desulfovibrio, Caloramator, and Sarcina [104, 105, 106, 107]. A study by Wang et al. [108] showed a decrease in Bifidobacterium spp. and mucolytic bacteria Akkermansia muciniphila in the gut microbiota of autism subjects compared to control subjects. Williams et al. [109] found an increase in the Firmicutes-to-Bacteroidetes ratio and a significant increase in Sutterella compared to their abundance in controls. These findings demonstrated that gut microbiota dysbiosis has close relationships with gastrointestinal and behavioral manifestations of autism” | concepts[159] |
| concept | exposure to stress — not defined in this paper's own words; experimental perturbation changing mouse microbiota — “The bidirectional interactions of gut–brain mean that the brain can also alter gut microbiota composition [110]. A model of social disruption among adult mice [111] demonstrated that exposure to stress results in substantial changes in gut microbiota composition: a decrease in Bacteroides spp. abundance and an increase in Clostridium spp. abundance have been observed in stress-induced mice relative to controls. The mechanisms by which stress influences gut microbiota composition are unclear but include microbial habitat alterations following stress-induced changes in intestinal mobility and mucin secretion [110, 112]. Other studies [62] revealed that chronic psychological stress is reflected in the microbiota composition. Indeed, depression due to chronic stressful life events is associated with an increase in Enterobacteriaceae, whereas psychological stress is associated with a reduction in Lactobacilli spp. and an increase in Escherichia coli and Pseudomonas spp. Gut microbiota variations are closely associated with the onset of these neurological disorders, and the gut bacterial communities may be a target for therapeutic interventions” | concepts[160] |
| concept | substantial changes in gut microbiota composition — not defined in this paper's own words; community outcome after stress exposure — “The bidirectional interactions of gut–brain mean that the brain can also alter gut microbiota composition [110]. A model of social disruption among adult mice [111] demonstrated that exposure to stress results in substantial changes in gut microbiota composition: a decrease in Bacteroides spp. abundance and an increase in Clostridium spp. abundance have been observed in stress-induced mice relative to controls. The mechanisms by which stress influences gut microbiota composition are unclear but include microbial habitat alterations following stress-induced changes in intestinal mobility and mucin secretion [110, 112]. Other studies [62] revealed that chronic psychological stress is reflected in the microbiota composition. Indeed, depression due to chronic stressful life events is associated with an increase in Enterobacteriaceae, whereas psychological stress is associated with a reduction in Lactobacilli spp. and an increase in Escherichia coli and Pseudomonas spp. Gut microbiota variations are closely associated with the onset of these neurological disorders, and the gut bacterial communities may be a target for therapeutic interventions” | concepts[161] |
| concept | intestinal mobility — not defined in this paper's own words; stress-sensitive habitat factor — “The bidirectional interactions of gut–brain mean that the brain can also alter gut microbiota composition [110]. A model of social disruption among adult mice [111] demonstrated that exposure to stress results in substantial changes in gut microbiota composition: a decrease in Bacteroides spp. abundance and an increase in Clostridium spp. abundance have been observed in stress-induced mice relative to controls. The mechanisms by which stress influences gut microbiota composition are unclear but include microbial habitat alterations following stress-induced changes in intestinal mobility and mucin secretion [110, 112]. Other studies [62] revealed that chronic psychological stress is reflected in the microbiota composition. Indeed, depression due to chronic stressful life events is associated with an increase in Enterobacteriaceae, whereas psychological stress is associated with a reduction in Lactobacilli spp. and an increase in Escherichia coli and Pseudomonas spp. Gut microbiota variations are closely associated with the onset of these neurological disorders, and the gut bacterial communities may be a target for therapeutic interventions” | concepts[162] |
| concept | mucin secretion — not defined in this paper's own words; stress-sensitive habitat factor — “The bidirectional interactions of gut–brain mean that the brain can also alter gut microbiota composition [110]. A model of social disruption among adult mice [111] demonstrated that exposure to stress results in substantial changes in gut microbiota composition: a decrease in Bacteroides spp. abundance and an increase in Clostridium spp. abundance have been observed in stress-induced mice relative to controls. The mechanisms by which stress influences gut microbiota composition are unclear but include microbial habitat alterations following stress-induced changes in intestinal mobility and mucin secretion [110, 112]. Other studies [62] revealed that chronic psychological stress is reflected in the microbiota composition. Indeed, depression due to chronic stressful life events is associated with an increase in Enterobacteriaceae, whereas psychological stress is associated with a reduction in Lactobacilli spp. and an increase in Escherichia coli and Pseudomonas spp. Gut microbiota variations are closely associated with the onset of these neurological disorders, and the gut bacterial communities may be a target for therapeutic interventions” | concepts[163] |
| concept | biomarker — not defined in this paper's own words; role proposed for dysbiosis across disorders — “Each healthy human is provided with unique gut microbiota. Core native microbiota are shaped in early life (4–36 months) by gut maturation developing from enterotype, birth gestational age, type of delivery, methods of milk feeding, weaning period, lifestyle, and dietary and cultural habits. After a child reaches 2–3 years old, a relative stability in gut microbiota composition has been demonstrated. Richness and diversity of gut microbiota shaped in early life characterize a healthy gut microbiota composition. However, this optimal healthy gut microbiota composition is different for each individual. Throughout life, the richer and more diverse the microbiota, the better they will withstand external threats. Indeed, gut microbiota represent a changing ecosystem that is severely tested by many factors such as unbalanced diet, stress, antibiotic use, or diseases. A healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. Indeed, disturbances to the delicate host–microbe relationship may disrupt the development of the immune system, which may in turn result in diseases [113]. Although the role of gut microbiota is still poorly understood, the close association between gut microbiota dysbiosis and intestinal and extra-intestinal disorders has been demonstrated. This is the reason why dysbiosis can be considered as a biomarker of such disorders and that the study of gut microbiota balances shall be one of the priorities for future therapies to prevent and treat diseases” | concepts[164] |
| concept | future therapies — not defined in this paper's own words; prevention and treatment work prioritizing microbiota balance — “Each healthy human is provided with unique gut microbiota. Core native microbiota are shaped in early life (4–36 months) by gut maturation developing from enterotype, birth gestational age, type of delivery, methods of milk feeding, weaning period, lifestyle, and dietary and cultural habits. After a child reaches 2–3 years old, a relative stability in gut microbiota composition has been demonstrated. Richness and diversity of gut microbiota shaped in early life characterize a healthy gut microbiota composition. However, this optimal healthy gut microbiota composition is different for each individual. Throughout life, the richer and more diverse the microbiota, the better they will withstand external threats. Indeed, gut microbiota represent a changing ecosystem that is severely tested by many factors such as unbalanced diet, stress, antibiotic use, or diseases. A healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. Indeed, disturbances to the delicate host–microbe relationship may disrupt the development of the immune system, which may in turn result in diseases [113]. Although the role of gut microbiota is still poorly understood, the close association between gut microbiota dysbiosis and intestinal and extra-intestinal disorders has been demonstrated. This is the reason why dysbiosis can be considered as a biomarker of such disorders and that the study of gut microbiota balances shall be one of the priorities for future therapies to prevent and treat diseases” | concepts[165] |
| concept | fermentation of galactooligosaccharide (GOS) — not defined in this paper's own words; Bifidobacterial process producing SCFAs — “Bifidobacterium_ spp. are responsible for the fermentation of galactooligosaccharide (GOS), one of the main components of breast milk, to produce SCFAs” | concepts[166] |
| concept | SCFAs — not defined in this paper's own words; short-chain fatty acids linked to barrier effects — “Daily exercise increases gut microbial diversity ( Table 2) with a Firmicutes enrichment microbiota: Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae by producing more SCFAs which may increase the expression of tight junction proteins in colon epithelia to heighten the resistance of the intestinal barrier, reduce mucosal permeability, and inhibit inflammatory cytokines” | concepts[167] |
| concept | imbalance between Firmicutes and Bacteroidetes — not defined in this paper's own words; phylum imbalance caused by broad-spectrum antibiotics — “Broad-spectrum antibiotics lead to an imbalance between Firmicutes and Bacteroidetes. The bacterial diversity decreases and so does the abundance of these bacteria during the treatments” | concepts[168] |
| concept | repeated disturbance — not defined in this paper's own words; repeated antibiotic perturbation — “This study revealed a considerable resilience to antibiotic administration but also suggested that, in some cases, the system retains a memory of past disturbance and that, in all cases, repeated disturbance leads to a persistent regime shift [48]. The impact of antibiotic disturbance on the resilience of microbiota during future antibiotic treatments” | concepts[169] |
| concept | gut microbial diversity — not defined in this paper's own words; community diversity increased by exercise — “Daily exercise increases gut microbial diversity ( Table 2) with a Firmicutes enrichment microbiota: Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae by producing more SCFAs which may increase the expression of tight junction proteins in colon epithelia to heighten the resistance of the intestinal barrier, reduce mucosal permeability, and inhibit inflammatory cytokines” | concepts[170] |
| concept | expression of tight junction proteins — not defined in this paper's own words; colon-barrier expression potentially increased by SCFAs — “Daily exercise increases gut microbial diversity ( Table 2) with a Firmicutes enrichment microbiota: Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae by producing more SCFAs which may increase the expression of tight junction proteins in colon epithelia to heighten the resistance of the intestinal barrier, reduce mucosal permeability, and inhibit inflammatory cytokines” | concepts[171] |
| concept | Celiac disease — not defined in this paper's own words; gluten-sensitive multifactorial intestinal disease — “Celiac disease is caused by the interplay between gluten, genetic factors, and environmental factors such as gut microbiota” | concepts[172] |
| concept | disturbances to the delicate host–microbe relationship — not defined in this paper's own words; perturbations proposed to disrupt immune development — “disturbances to the delicate host–microbe relationship may disrupt the development of the immune system, which may in turn result in diseases” | concepts[173] |
| concept | diseases — not defined in this paper's own words; downstream outcomes proposed after host-microbe disturbance — “disturbances to the delicate host–microbe relationship may disrupt the development of the immune system, which may in turn result in diseases” | concepts[174] |
| concept | diversity and abundance of the microbiome — not defined in this paper's own words; outputs highlighted by 16S profiling — “The human gastrointestinal (GI) tract contains an abundant and diverse microbial community that gathers more than 100 trillion microorganisms [1]. The density of bacterial cells in the colon has been estimated at 1011 to 1012 per milliliter which makes the colon one of the most densely populated microbial habitats known on earth [2]. The gut microbiome encodes over 3 million genes producing thousands of metabolites, whereas the human genome consists of approximately 23,000 genes [3]. For years, scientists have been interested in gut microbiota, but one of the major difficulties in the relevant research has been the ability to culture these microorganisms [4]. During the last years, new technologies have allowed researchers to phylogenetically identify and/or quantify the components of the gut microbiota by analyzing nucleic acids (DNA and RNA) directly extracted from stools. The majority of these techniques are based on the extraction of DNA and the amplification of the 16S ribosomal RNA gene (rRNA) [5, 6]. 16S rRNA sequencing has become the most useful technique to highlight diversity and abundance of the microbiome. The 16S rRNA gene sequences can be exploited with polymerase chain reaction (PCR) and metagenomics sequencing to characterize the microbial strains” | concepts[175] |
| concept | beneficial bacteria — not defined in this paper's own words; infant-colonizing bacteria favored by lactoferrin — “Lactoferrin (LF) is another well-known component of human milk favoring gut infant colonization with beneficial bacteria and consequently representing a crucial role played in preterm infants’ microbiota [22]. Indeed, correlations between LF and beneficial microbiota in breast milk and infant’s feces have been demonstrated [22]. High levels of fecal LF, particularly in preterm infants, may represent an important factor in the initiation, development, and/or composition of the neonatal gut microbiota contributing to the immunologic maturation and well-being of the newborn, especially in preterm infants [22]. Therefore, a mother’s own milk helps to shape developing core gut microbiota that can improve growth and neurodevelopment and decrease the risk of NEC and late-onset sepsis [19, 21]. It is for all these reasons that human milk should be the primary enteral diet of premature infants” | concepts[176] |
| concept | distinctive way of generating energy from fermentable substrates — not defined in this paper's own words; enterotype-specific functional energy strategy — “Gut microbiota of each individual are specifically characterized by clusters of bacteria named enterotypes [13]. Three enterotypes are characterized by three dominant bacteria clusters ( Table 2): Bacteroides (enterotype I), Prevotella (enterotype II), or Ruminococcus (enterotype III). Each enterotype harbors different bacteria genera ( Table 1). These three enterotypes are not only enumerations of bacteria; they are also specifically regrouped by functions. Indeed, an enterotype is a functional harmonious association of several bacteria species rather than a systematic addition of bacteria species. Every enterotype is not a clear-cut identity such as blood groups; however, enterotypes characterize individuals, remain stable from adulthood, and can be restored if they are modified. Each enterotype with its distinctive clusters of bacteria and respective functional characteristics defines a distinctive way of generating energy from fermentable substrates available in the colon. Indeed, bacteria clusters of enterotype I derive energy primarily from carbohydrates using principally glycolysis and pentose phosphate pathways, whereas bacteria clusters of enterotypes II and III are able to degrade mucin glycoproteins of the gut mucosal layer. Enterotypes seem to be principally defined according to dietary habits. Understanding the origins and functions of enterotypes may improve the knowledge of the relationships between gut microbiota and human health” | concepts[177] |
| concept | BMI levels — not defined in this paper's own words; body-mass classes assigned predictive value — “have examined the impact of childhood BMI on gut microbiota composition and demonstrated that children with overweight or normal BMI are provided with a higher microbial diversity than underweight children. Gut microbiota diversity descends stepwise based on BMI class [50, 52]. Bervoets et al. [53] demonstrated that the microbiota of obese children are provided with an elevated Firmicutes-to-Bacteroidetes ratio compared to the microbiota of lean children [53]. Furthermore, low relative proportions of Bifidobacterium vulgatus and high concentrations of Lactobacillus spp. are observed in the obese microbiota [53]. Riva et al. [54] confirmed that obesity is associated with elevated levels of Firmicutes such as Ruminococcaceae and depleted levels of Bacteroidetes such as Bacteroidaceae and Bacteroides. SCFAs are higher in obese children suggesting elevated substrate utilization. These findings suggest that the dysbiosis of gut microbiota may contribute to the pathophysiology of obesity and the increased ratio of Firmicutes to Bacteroidetes is associated with the increased production of SCFAs and energy harvest from colonic fermentation [54]. The underweight BMI level also revealed profound gut microbiota variations. Borgo et al. [55] performed a comprehensive data analysis comparing gut microbiota and anthropometric traits of 15 anorexia nervosa (AN) women and healthy controls. Results showed that AN intestinal microbiota showed a significant increase in Enterobacteriaceae and Methanobrevibacter smithii compared with healthy controls [55]. On the contrary, the genera Roseburia, Ruminococcus, and Clostridium were depleted in line with the observed reduction in AN of the total SCFAs [55]. BMI levels represent a valid predictive value for gut microbiota dysbiosis. Studies have demonstrated that gut microbiota variations are correlated with increased or depleted production of SCFAs that may respectively contribute to the pathophysiology of obesity or AN. Interventions such as prebiotics and probiotics may be possible solutions to manage both pediatric obesity” | concepts[178] |
| concept | gut microbiota dysbiosis — not defined in this paper's own words; community imbalance predicted by BMI levels — “have examined the impact of childhood BMI on gut microbiota composition and demonstrated that children with overweight or normal BMI are provided with a higher microbial diversity than underweight children. Gut microbiota diversity descends stepwise based on BMI class [50, 52]. Bervoets et al. [53] demonstrated that the microbiota of obese children are provided with an elevated Firmicutes-to-Bacteroidetes ratio compared to the microbiota of lean children [53]. Furthermore, low relative proportions of Bifidobacterium vulgatus and high concentrations of Lactobacillus spp. are observed in the obese microbiota [53]. Riva et al. [54] confirmed that obesity is associated with elevated levels of Firmicutes such as Ruminococcaceae and depleted levels of Bacteroidetes such as Bacteroidaceae and Bacteroides. SCFAs are higher in obese children suggesting elevated substrate utilization. These findings suggest that the dysbiosis of gut microbiota may contribute to the pathophysiology of obesity and the increased ratio of Firmicutes to Bacteroidetes is associated with the increased production of SCFAs and energy harvest from colonic fermentation [54]. The underweight BMI level also revealed profound gut microbiota variations. Borgo et al. [55] performed a comprehensive data analysis comparing gut microbiota and anthropometric traits of 15 anorexia nervosa (AN) women and healthy controls. Results showed that AN intestinal microbiota showed a significant increase in Enterobacteriaceae and Methanobrevibacter smithii compared with healthy controls [55]. On the contrary, the genera Roseburia, Ruminococcus, and Clostridium were depleted in line with the observed reduction in AN of the total SCFAs [55]. BMI levels represent a valid predictive value for gut microbiota dysbiosis. Studies have demonstrated that gut microbiota variations are correlated with increased or depleted production of SCFAs that may respectively contribute to the pathophysiology of obesity or AN. Interventions such as prebiotics and probiotics may be possible solutions to manage both pediatric obesity” | concepts[179] |
| concept | intestinal and extra-intestinal disorders — not defined in this paper's own words; disease classes associated with dysbiosis — “Each healthy human is provided with unique gut microbiota. Core native microbiota are shaped in early life (4–36 months) by gut maturation developing from enterotype, birth gestational age, type of delivery, methods of milk feeding, weaning period, lifestyle, and dietary and cultural habits. After a child reaches 2–3 years old, a relative stability in gut microbiota composition has been demonstrated. Richness and diversity of gut microbiota shaped in early life characterize a healthy gut microbiota composition. However, this optimal healthy gut microbiota composition is different for each individual. Throughout life, the richer and more diverse the microbiota, the better they will withstand external threats. Indeed, gut microbiota represent a changing ecosystem that is severely tested by many factors such as unbalanced diet, stress, antibiotic use, or diseases. A healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. Indeed, disturbances to the delicate host–microbe relationship may disrupt the development of the immune system, which may in turn result in diseases [113]. Although the role of gut microbiota is still poorly understood, the close association between gut microbiota dysbiosis and intestinal and extra-intestinal disorders has been demonstrated. This is the reason why dysbiosis can be considered as a biomarker of such disorders and that the study of gut microbiota balances shall be one of the priorities for future therapies to prevent and treat diseases” | concepts[180] |
| concept | brain — not defined in this paper's own words; central side of bidirectional gut-brain interaction — “The brain and the gut are connected via the gut–brain axis with bidirectional interactions between the central nervous system, the enteric nervous system, and the gastrointestinal tract. These bidirectional interactions enable the brain to influence gastrointestinal functions as well as immune functions” | concepts[181] |
| concept | gut — not defined in this paper's own words; gastrointestinal side of bidirectional gut-brain interaction — “The brain and the gut are connected via the gut–brain axis with bidirectional interactions between the central nervous system, the enteric nervous system, and the gastrointestinal tract. These bidirectional interactions enable the brain to influence gastrointestinal functions as well as immune functions” | concepts[182] |
| concept | gut bacterial communities — not defined in this paper's own words; communities proposed as therapeutic targets — “The bidirectional interactions of gut–brain mean that the brain can also alter gut microbiota composition [110]. A model of social disruption among adult mice [111] demonstrated that exposure to stress results in substantial changes in gut microbiota composition: a decrease in Bacteroides spp. abundance and an increase in Clostridium spp. abundance have been observed in stress-induced mice relative to controls. The mechanisms by which stress influences gut microbiota composition are unclear but include microbial habitat alterations following stress-induced changes in intestinal mobility and mucin secretion [110, 112]. Other studies [62] revealed that chronic psychological stress is reflected in the microbiota composition. Indeed, depression due to chronic stressful life events is associated with an increase in Enterobacteriaceae, whereas psychological stress is associated with a reduction in Lactobacilli spp. and an increase in Escherichia coli and Pseudomonas spp. Gut microbiota variations are closely associated with the onset of these neurological disorders, and the gut bacterial communities may be a target for therapeutic interventions” | concepts[183] |
| concept | therapeutic interventions — not defined in this paper's own words; interventions targeting gut communities — “The bidirectional interactions of gut–brain mean that the brain can also alter gut microbiota composition [110]. A model of social disruption among adult mice [111] demonstrated that exposure to stress results in substantial changes in gut microbiota composition: a decrease in Bacteroides spp. abundance and an increase in Clostridium spp. abundance have been observed in stress-induced mice relative to controls. The mechanisms by which stress influences gut microbiota composition are unclear but include microbial habitat alterations following stress-induced changes in intestinal mobility and mucin secretion [110, 112]. Other studies [62] revealed that chronic psychological stress is reflected in the microbiota composition. Indeed, depression due to chronic stressful life events is associated with an increase in Enterobacteriaceae, whereas psychological stress is associated with a reduction in Lactobacilli spp. and an increase in Escherichia coli and Pseudomonas spp. Gut microbiota variations are closely associated with the onset of these neurological disorders, and the gut bacterial communities may be a target for therapeutic interventions” | concepts[184] |
Statistics — cross-field join keys
field-invariant statistical terms, used in their statistical sense (gated on a number / symbol / test). A p-value or a standard deviation means the SAME thing in physics, biology, psychology and sociology — so these are the strongest cross-field join keys. Grounded verbatim.
| density | — “The density of bacterial cells in the colon has been estimated at 1011 to 1012 per milliliter which makes the colon one of the most densely populated microbial habitats known on earth” | content_tags.statistics[0] |
Full text — tagged
The reference list is not part of the text we hold for this paper. Our copy was extracted from the publisher's page and the bibliography did not survive that extraction, so the article below ends before its references. Nothing has been removed by us.
# Abstract Each individual is provided with a unique gut microbiota profileterm that plays many specific functions in host nutrient metabolismterm, maintenance of structural integrity of the gut mucosal barrierterm, immunomodulationterm, and protection against pathogensterm. Gut microbiotaterm are composed of different bacteria speciesterm taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiotaterm are shaped in early life as their composition depends on infant transitionsterm (birth gestational date, type of deliveryterm·var, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiotaterm remain relatively stable in adulthood but differ between individuals due to enterotypesterm, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habitsterm. Accordingly, there is not a unique optimal gut microbiotaterm composition since it is different for each individual. However, a healthy host–microorganism balanceterm must be respected in order to optimally perform metabolic and immune functionsterm and prevent diseaseterm development. This reviewterm·mth will provide an overview of the studies that focus on gut microbiotaterm balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiotaterm variations and diseasesterm. Indeed, dysbiosisterm of gut microbiotaterm is associated not only with intestinal disorders but also with numerous extra-intestinal diseasesterm such as metabolic and neurological disorders. Understanding the cause or consequenceterm of these gut microbiotaterm balances in health and diseaseterm and how to maintain or restore a healthy gut microbiotaterm composition should be useful in developing promising therapeutic interventionsterm.
Keywords: gut microbiotaterm, diversityterm, health, diet, nutrition, age, milk feeding, necrotizing enterocolitis, weaning, enterotypesterm, irritable bowel syndrome, inflammatory bowel diseaseterm, celiac diseaseterm, colorectal cancerterm, obesity, type 2 diabetesterm, Alzheimer’s diseaseterm, Parkinson’s diseaseterm, hepatic encephalopathy, autism spectrum disordersterm, personalized medicine 1. Introduction The human gastrointestinal (GI) tractterm contains an abundant and diverse microbial community that gathers more than 100 trillion microorganisms [1]. The density of bacterial cells in the colon has been estimated at 1011 to 1012 per milliliter which makes the colon one of the most densely populated microbial habitats known on earth [2]. The gut microbiometerm encodes over 3 million genes producing thousands of metabolitesterm, whereas the human genometerm consists of approximately 23,000 genes [3]. For years, scientists have been interested in gut microbiotaterm, but one of the major difficulties in the relevant research has been the ability to culture these microorganisms [4]. During the last years, new technologies have allowed researchers to phylogenetically identify and/or quantify the components of the gut microbiotaterm by analyzing nucleic acids (DNA and RNAterm) directly extracted from stools. The majority of these techniques are based on the extraction of DNA and the amplification of the 16S ribosomal RNA gene (rRNA)term [5, 6]. 16S rRNA sequencingterm has become the most useful technique to highlight diversity and abundance of the microbiometerm. The 16S rRNA gene sequences can be exploited with polymerase chain reaction (PCR)term and metagenomics sequencingterm to characterize the microbial strains [7].
Considering the characteristics of gut microbiotaterm such as the large diversityterm, the stability and resilienceterm, and the symbiotic interaction with the hostterm, we can define the host and the microorganisms inhabiting itterm as a “superorganismterm” [8, 9] which performs immune and metabolic functions [1]. Gutterm bacteria are key regulators of digestion along the gastrointestinal tract; commensal bacteriaterm play an important role in the extraction, synthesis, and absorption of many nutrients and metabolitesterm, including bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs)term. Gut microbiotaterm have a crucial immune function against pathogenic bacteria colonizationterm inhibiting their growth, consuming available nutrients and/or producing bacteriocins. Gut microbiotaterm also prevent bacteria invasion by maintaining the intestinal epithelium integrityterm [10]. Microorganisms prevent pathogenic colonization by many competition processes: nutrient metabolismterm, pH modificationterm, antimicrobial peptide secretionsterm, and effects on cell signaling pathwaysterm. Moreover, recent studies have identified a critical role for commensal bacteriaterm and their products in regulating the development, homeostasis, and function of innate and adaptive immune cellsterm [11]. It is paradoxical to note that the gut microbiotaterm functions are highly preserved between individuals, whereas each individual’s gut microbiotaterm are characterized by a specific combination of bacterial species due to inter-individual and intra-individual variationsterm throughout human life.
This reviewterm·mth aims to define what would be the optimal gut microbiotaterm composition in order to maintain these optimal microbiota immune and metabolic functions. After defining microbiota variations within and between individuals, we highlight the involvement of gut microbiota dysbiosisterm in various intestinal and extra-intestinal disorderterm development and we describe the strong relationship between gut microbiotaterm diversityterm and health. We will see how these gut microbiotaterm variations may have huge implications for intestinal and extra-intestinal disordersterm and, consequently, may influence health.
2. Gut Microbiotaterm Variations Gut microbiotaterm are composed of several species of microorganisms, including bacteria, yeast, and virusesterm. Taxonomically, bacteria are classified according to phyla, classes, orders, families, genera, and species. Only a few phyla are represented, accounting for more than 160 species [12]. The dominant gutterm microbial phyla are Firmicutesterm, Bacteroidetesterm, Actinobacteriaterm, Proteobacteriaterm, Fusobacteriaterm, and Verrucomicrobiaterm, with the two phyla Firmicutesterm and Bacteroidetesterm [13] representing 90% of gut microbiotaterm. The Firmicutes phylumterm is composed of more than 200 different genera such as Lactobacillus, Bacillus, Clostridiumterm, Enterococcus, and Ruminicoccus. Clostridiumterm genera represent 95% of the Firmicutesterm phyla. Bacteroidetesterm consists of predominant genera such as Bacteroidesterm and Prevotellaterm. The Actinobacteriaterm phylum is proportionally less abundant and mainly represented by the Bifidobacteriumterm genus [13]. Examples of taxonomic gut microbiotaterm composition are illustrated in Figure 1.
Figure 1.
 Examples of taxonomic gut microbiotaterm composition. In the box are cited examples of bacteria belonging to Phyla Firmicutesterm and Bacteroidetesterm, representing 90% of gut microbiotaterm.
2.1. Variations in the Same Individual Human gut microbiotaterm vary taxonomically and functionally in each part of the GI tract and undergo variations in the same individual due to infant transitionsterm, age, and environmental factors such as antibiotic use. Microbiota variations within individuals are summarized in Table 1.
Table 1.
Microbiota variations within individuals.
| | | Gut Microbiotaterm Abundance | Bacteria Diversityterm | Ref. | | :-: | :-: | :-: | :-: | :-: | | | | Actinobacteriaterm | Bacteroidetesterm | Firmicutesterm | Proteobacteriaterm | Fusobacteriaterm | Verrucomicrobiaterm | Euryarchaeota | | :-: | :-: | :-: | :-: | :-: | :-: | :-: | :-: | :-: | | Anatomical part of gutterm tract | Small intestineterm | | | Lactobacillus | Enterobacteriaceaeterm * | | | | | [14] | | Colon | | Bacteroidaceae *<br>Prevotellaceae *<br>Rikenellaceae * | Lachnospiraceae *<br>Ruminococcaceae * | | | | | | | | Gestational age | Preterm birth (<37 weeks of gestation) | Bifidobacteriumterm spp.↓<br>Atopobium spp.↓ | Bacteroidesterm *↓ (non-secretor mothers) | Firmicutesterm *↓ (non-secretor mothers)<br>Lactobacillus ↑<br>Ruminococcus spp.<br>Lachnospiraceae *<br>Peptostreptococcaceae *<br>Clostridiaceae * | Enterobacteriaceaeterm *↑<br>Enterococcus spp.↑ | | | | ↓ | [15, 16, 19] | | Full-term birth | Bifidobacteriumterm spp.↑ | Bacteroidetesterm *↑ | Ruminococcus spp.<br>Lachnospiraceae *<br>Peptostreptococcaceae *<br>Clostridiaceae * | Enterobacteriaceaeterm * | | | | ↑ | [16, 20] | | Type of deliveryterm·var | Vaginal deliveryterm | Bifidobacteriumterm spp.↑<br>Bifidobacteriumterm longum ↑<br>Bifidobacteriumterm catenulatum ↑ | Prevotellaterm ↑<br>Bacteroidesterm fragilis ↑ | Lactobacillus ↑<br>Staphylococcus ↑<br>Streptococcus ↑ | Escherichia ↑ | Sneathia ↑ | | | ↑ | [22, 23, 24, 25, 26] | | C-section | Corynebacterium ↑<br>Propionibacterium ↑ | Bacteroidesterm *↓ | Staphylococcus ↑ | Escherichia ↓<br>Shigella ↓ | | | | ↓ | [21, 22, 23, 27] | | Methods of (milk) feedings | Breast milk | Bifidobacteriumterm ↑↑ | | Lactobacillus ↑<br>Staphylococcus ↑ | Enterococcus ↑ | | | | ↑ | [27, 30, 31, 32, 38] | | Artificial milk | Bifidobacteriumterm ↑ | Bacteroidesterm ↑ | Clostridiumterm ↑<br>Clostridiumterm difficile ↑<br>Lactobacillus ↑ | Escherichia ↑ | | | | ↓ | [27, 30, 31, 32] | | Introduction of solid foodterm | Bifidobacteriumterm ↑ | Bacteroidetesterm *↑<br>Bacteroidesterm ↑ | Firmicutesterm *↑<br>Lactobacilli↑<br>Clostridiumterm coccoides ↑ | | | | | ↑ | [36, 37] | | Human age | Childhood (first year of life) | Bifidobacteriumterm | Bacteroidesterm | Veillonella<br>C. coccoides<br>C. botulinum | | | Akkermansia muciniphilaterm | | ↑ | [38, 39] | | 2–3 years old to adult | Bifidobacteriaceae *<br>Coriobacteriaceae * | Bacteroidaceae *<br>Prevotellaceae *<br>Rikenellaceae * | Lachnospiraceae<br>Ruminococcaceae | Proteobacteriaterm * | Fusobacteriaterm * | Akkermansia muciniphilaterm | Methanobrevibacter smithii | ↑ | [38] | | Over 70 | Bifidobacteriaceae ↓ | | Clostridiumterm *↓ | Proteobacteriaterm *↑ | | | | ↓ | [40] | | Antibiotic treatmentsterm | Macrolide | Actinobacteriaterm *↓ | Bacteroidesterm ↑ | Firmicutesterm *↓ | Proteobacteriaterm *↑ | | | | ↓ | [43] | | Clarithromycin | Actinobacteriaterm *↓ | Bacteroidesterm ↑ | Firmicutesterm *↓ | Proteobacteriaterm *↑ | | | | ↓ | | Vancomycin | | | Lactobacillus ↓<br>Clostridiumterm ↓ | | | | | ↓ | | Ciprofloxacin | Bifidobacteriumterm ↓ | Alistipes ↓<br>Bacteroidesterm↑ | Faecalibacterium ↓<br>Oscillospira ↓<br>Ruminococcus ↓<br>Dialister ↓ | | | | | ↓ | | Clindamycin | Bifidobacteriaceae ↓<br>Lactobacillus ↓ | | | | | | | ↓ | \* Unknown genera.
2.1.1. Intestine Anatomical Regions Gut microbiotaterm vary according to the intestine anatomical regions, which vary in terms of physiology, pH and O2 tension, digesta flow rates (rapid in the mouth to the caecum, slower afterward), substrate availability, and host secretions [14]. The small intestineterm provides a more challenging environment for microbial colonizers given the fairly short transit timesterm (3–5 h) and the high bile concentrationsterm. The large intestineterm, which is characterized by slow flow rates and neutral to mildly acidic pH, harbors by far the largest microbial community (dominated by obligate anaerobic bacteriaterm) [14]. We can observe a microbiota quantitative increasing gradientterm and a microbiota qualitative decreasing gradientterm with a progressive aerobic bacteria decrease for the benefit of strictly anaerobic bacteria ( Table 1).
2.1.2. Infant Transitionsterm ##### Birth Gestational Ageterm Birth gestational ageterm is a major determinant of gut microbiotaterm colonization. The microbiota composition of preterm infantsterm (<37 weeks of gestation) is different from term counterparts ( Table 1). In preterm infantsterm, after birth, the microbiota colonization is challenged by organ immaturityterm and environmental factors such as antibiotic use, hospital stay [15], and enteral feeding [16]. For these reasons, the postnatal maturation of gut and systemic immunityterm may be highly affected by preterm birth [16].
In a new-born pig model, an analysis of the gut microbiotaterm composition of preterm and term pigs showed that Ruminococcus spp., some Enterobacterium spp., Lachnospiraceae, Peptostreptococcaceae, and Clostridiaceae were dominant genera in both preterm and term pigs. However, a higher Enterococcus spp. abundance in preterm than term pigs was found [16].
Preterm infantsterm show low diversityterm with an increased colonization of potentially pathogenic bacteria from the Enterobacteriaceaeterm family of the Proteobacteriaterm phylum [15] and reduced levels of strict anaerobesterm such as Bifidobacteriumterm [17], Bacteroidesterm, and Atopobium [15].
Human milk composition depends on genetic factors and the mother’s secretor and Lewis blood groupsterm defining four phenotypes characterized by different levels of oligosaccharide amounts [18]. Higher levels of Proteobacteriaterm and lower levels of Firmicutesterm are noted in premature infants of non-secretor mothers [19]. A recent study by Praticò et al. [20] characterizing human breast milk composition demonstrated that human milk oligosaccharides (HMOs)term related to different mother phenotypes modulate gut microbiotaterm composition in infants. Specifically, HMOs associated with secretor mothersterm may have a protective prebiotic effectterm by decreasing pathogens associated with sepsisterm and necrotizing enterocolitis (NEC)term [19]. This indicates that HMOs may influence the intestinal microbiota and prevent gutterm dysfunction and NEC in preterm infantsterm [21].
Lactoferrin (LF)term is another well-known component of human milk favoring gutterm infant colonization with beneficial bacteriaterm and consequently representing a crucial role played in preterm infantsterm’ microbiota [22]. Indeed, correlations between LF and beneficial microbiota in breast milk and infant’s feces have been demonstrated [22]. High levels of fecal LF, particularly in preterm infantsterm, may represent an important factor in the initiation, development, and/or composition of the neonatal gut microbiotaterm contributing to the immunologic maturation and well-being of the newborn, especially in preterm infantsterm [22].
Therefore, a mother’s own milkterm helps to shape developing core gut microbiotaterm that can improve growth and neurodevelopment and decrease the risk of NEC and late-onset sepsisterm [19, 21]. It is for all these reasons that human milk should be the primary enteral diet of premature infants.
##### Type of Deliveryterm·var At birth, the intestine is sterile and devoid of bacteria. After birth, a rich and dynamic ecosystem develops from mother’s skin, vaginal and fecal microbiota, and environment microbiota contacts. Microbiota colonization varies according to the type of deliveryterm·var [23, 24, 25] ( Table 1).
With regard to vaginal deliveryterm, newborns acquire a microbiota composition resembling their mother’s vaginal microbiotaterm. Indeed, an analysis of the meconium of newborn infants [24] revealed a strong correlation between the microbiota of the newborn digestive tract and the microbial communities of the mother’s vagina: Lactobacillus, Prevotellaterm, and Sneathia. Biasucci et al. [25] showed that the microbiota of vaginally delivered infants are also characterized by predominant groups such as Bifidobacteriumterm longum and Bifidobacteriumterm catenulatum. Other facultative anaerobic species such as Escherichia coli, Staphylococcus, Bacteroidesterm fragilis, and Streptococcus colonize the infant gutterm [26, 27, 28].
On the contrary, infants born by cesarean section (C-section)term acquire bacteria derived from hospital environmentterm and mother’s skin: Staphylococcus, Corynebacterium, Propionibacterium spp. [24, 29]. Escherichia, Shigella, and Bacteroidesterm species are underrepresented in infants born by cesarean delivery [29]. The intestinal microbiota of neonates delivered by cesarean delivery are less diverse in terms of bacteria speciesterm than the microbiota of vaginally delivered infants [25].
Differences between the microbiota of C-section and vaginally born infants have been also detected in analyses performed at 7 years of age [23]. Cesarean birth has been associated with an increased risk of chronic immune disorders such as asthma, systemic connective tissue disorders, juvenile arthritis, inflammatory bowel diseaseterm [30], and obesity [31].
##### Methods of Milk Feeding Studies have demonstrated that formula-fed infantsterm are more often colonized with Escherichia coli, Bacteroidesterm, and Clostridiumterm difficile compared with breastfed infantsterm [29, 32]. Regarding Actinobacteriaterm abundance, Bifidobacteriumterm spp. have been associated with breastfeeding and formula milk [33, 34]. However, breastfed infantsterm generally harbor a more complex and diverse Bifidobacteriumterm microbiota than formula-fed infantsterm [34]. Breastfed infantsterm are provided with microbiota having more than a two-fold increase in the number of Bifidobacteriumterm cells compared to formula-fed infantsterm [33]. Breastfed infantsterm have more beneficial gut microbiotaterm, with a higher richness and diversityterm of Bifidobacteriumterm spp. and a lower number of Clostridiumterm difficile and Escherichia coli than formula-fed infantsterm [32] ( Table 1).
Bifidobacteriumterm spp. are responsible for the fermentation of galactooligosaccharide (GOS)term, one of the main components of breast milk, to produce SCFAsterm [35]. Indeed, Bifidobacteriumterm spp. have an enzyme named lacto-N-biosidaseterm, which facilitates the assimilation of GOS [36]. If Bifidobacteriumterm quantity increases, the quantity of HMOs in feces decreases causing elevated acetate and lactate concentrations and decreasing pH [37]; an HMO consumptionterm by Bifidobacteria in the infant’s gutterm may suggest a prebiotic effect of HMOs on gutterm infant microbiota by selectively stimulating Bifidobacteriumterm spp. [37]. Another prebiotic effect of β-palmitateterm, a natural human milk fatty acid and a component of some infant formulas, on gutterm infant microbiota was demonstrated by positively influencing Bifidobacteriumterm spp. (and Lactobacillus spp.) abundance [38].
Furthermore, the maintenance of a healthy and balanced mother’s gut microbiotaterm during pregnancy is also considered as an important factor in positively influencing the milk microbiota composition [39]. Additionally, oral probiotic supplementation in mothers with vaginal deliveryterm may increase breast milk Bifidobacteriumterm spp. and Lactobacilli spp. abundance [39].
These studies have shown that native core microbiotaterm·def are shaped during early life: the profile of intestinal microbiota in the full-term, vaginally delivered, and breastfed infantterm with healthy and balanced mother’s milk microbiota is considered healthy. Researches should seek to demonstrate the role of this native core microbiotaterm·def composition on gutterm health and subsequent diseasesterm.
##### Weaning Period The introduction of solid foodsterm and the termination of milk-feeding/weaning coincide with major gut microbiotaterm changes. The abundance of genera Bifidobacteriumterm, Clostridiumterm coccoides, and Bacteroidesterm are predominant after weaning [40]. The microbiota of breastfed children and the microbiota of children previously fed with formula milk become closer to each other ( Table 1).
Dietary habitsterm, infant weaning, and feeding practices become determinants and play a crucial role in gut microbiotaterm variations. The introduction of high-fiber and carbohydrate foodsterm (traditional foods) causes an increase in Firmicutesterm and Prevotellaterm, whereas the introduction of high-fiber and animal protein foodsterm causes an increase in Bacteroidetesterm [41]. Furthermore, Fallani et al. [40] demonstrated that northern European countries are associated with a higher proportion of Bifidobacteria in the infant gut microbiotaterm, whereas higher levels of Bacteroidesterm and Lactobacilli characterize southern European countries.
2.1.3. Age At one year old, a child’s microbiota composition has a characteristic abundance of Akkermansia muciniphilaterm, Bacteroidesterm, Veillonella, Clostridiumterm coccoides spp., and Clostridiumterm botulinum spp. [42].
Microbiota diversityterm increases with age until it becomes a stable adult microbiota compositionterm dominated by three bacterial phyla ( Table 1): Firmicutesterm ( Lachnospiraceae and Ruminococcaceae), Bacteroidetesterm ( Bacteroidaceae, Prevotellaceae, and Rikenellaceae), and Actinobacteriaterm ( Bifidobacteriaceae and Coriobacteriaceae) that are the result of maturation due to the influence of genetics, environment, diet, lifestyle, and gut physiologyterm [42]. At approximately three years of age, a child’s gut microbiotaterm composition and diversityterm are most like those of adults [43].
With regard to older people over the age of 70term, gut microbiotaterm composition can be affected by digestion and nutrient absorption changes and immune activity weakness. Dietary habitterm changes (more monotonous) may also weaken gut microbiotaterm diversityterm. A decrease in anaerobic bacteria such as Bifidobacteriumterm spp. and an increase in Clostridiumterm and Proteobacteriaterm have been observed [44]. Given the role of Bifidobacteriumterm spp. in the stimulation of the immune system and metabolic processes, a Bifidobacteria decrease may partially explain low systemic inflammatory status and malnutrition in older adults [45].
2.1.4. Antibiotics Gut microbiotaterm composition can be more or less affected by antibiotic use. A follow-up study explored the effect of antibiotics with different modes of action on human gut microbiotaterm composition [46] and demonstrated that antibiotic treatmentsterm modify the gut microbiotaterm composition with an abundance/appearance of certain species and a decrease/disappearance of other species ( Table 1). Broad-spectrum antibioticsterm lead to an imbalance between Firmicutes and Bacteroidetesterm. The bacterial diversityterm decreases and so does the abundance of these bacteria during the treatments. The alteration of microbiome composition depends on the antibiotic class, dose, period of exposure, pharmacological action, and target bacteriaterm [47] ( Table 1). Specific properties of antibiotics such as antimicrobial effects or mode of action are powerful forces for the selection of intestinal microbiota and are partially responsible for the shifts in bacterial composition during antibiotic therapy [46].
Each class of antibiotics has different properties and excretion systems, resulting in different patterns of alteration in the microbiome composition [47].
A cultivation-independent survey of gut microbiotaterm composition of three persons before, during, and after two exposures to the same antibiotic (ciprofloxacin) [48] has been conducted. This study revealed a considerable resilience to antibiotic administration but also suggested that, in some cases, the system retains a memory of past disturbanceterm and that, in all cases, repeated disturbanceterm leads to a persistent regime shiftterm [48]. The impact of antibiotic disturbance on the resilience of microbiota during future antibiotic treatmentsterm can thus also vary considerably across individuals [49].
2.2. Gut Microbiotaterm Variations between Individuals We highlighted that the gut microbiotaterm composition varies in the same individual and we will see that it also changes between individuals. These inter-individual variationsterm are principally due to enterotypesterm, body mass index (BMI) level, and external factors such as lifestyle, exercise frequency, ethnicity, and dietary and cultural habits. The microbiota abundance variations between individuals are illustrated in Table 2.
Table 2.
Microbiota variations between individuals.
| | | Gut Microbiotaterm Abundance | Bacteria Diversityterm | Ref. | | :-: | :-: | :-: | :-: | :-: | | | | Actinobacteriaterm | Bacteroidetesterm | Firmicutesterm | Proteobacteriaterm | Verrucomicrobiaterm | Euryarchaeota | Spirochaetes | | :-: | :-: | :-: | :-: | :-: | :-: | :-: | :-: | :-: | | Enterotypeterm | I | Slackia | Bacteroidesterm(1)<br>Parabacteroides | Clostridiales *<br>Alkaliphilus<br>Lactobacillus<br>Catenibacterium | Geobacter | | Methanobrevibacter smithii | | | [13] | | II | Eggerthella | Prevotellaterm(1) | Veillonella<br>Ruminococcaceae *<br>Holdemania<br>Peptostreptococcaceae *<br>Staphylococcus<br>Leuconostoc | Desulfovibrionaceae *<br>Rhodospirillum<br>Helicobacter<br>Escherichia<br>Shigella | Akkermansia muciniphilaterm | | | | | III | Gordonibacter | Sphingobacterium | Ruminococcus(1)<br>Staphylococcus<br>Marvinbryantia<br>Symbiobacterium<br>Ruminococcaceae *<br>Dialister | | Akkermansia muciniphilaterm | | | | | BMI levelterm (among children and adolescents) | Overweight to obese level | Bifidobacteriumterm ↑<br>B. vulgatus ↓ | Bacteroidetesterm *↓ | Lactobacillus ↑<br>Firmicutesterm *↑ | Proteobacteriaterm *↑ | | | | ↓ | [46, 47, 49, 50] | | Underweight level | | | Roseburia spp.↓<br>Ruminococcus↓<br>Clostridiumterm spp.↓ | Enterobacteriaceaeterm *↑ | | Methanobrevibacter smithii ↑ | | ↓ | [46, 51] | | Exercise frequency | High performance sport | | Bacteroidesterm ↓ | Ruminococcaceae *↑<br>Lactobacillus ↓<br>Lactobacillaceae *↓ | Succinivibrionaceae *↑ | Akkermansiaceae ↓ | | | ↑ | [57] | | Children and adolescents daily exerciseterm | | | Clostridiales ↑<br>Roseburia ↑<br>Lachnospiraceae ↑<br>Erysipelotrichaceae ↑ | | | | | ↑ | [46] | | Type of diet, communities, climate, and geographical sites | High-fiber diet (African dietterm) | Bifidobacteriumterm ↓ | Prevotellaterm ↑<br>Bacteroidesterm ↓ | Eubacterium ↑<br>Oscillibacter ↑<br>Butyricicoccus ↑<br>Sporobacter ↑<br>Blautia ↓<br>Dorea ↓<br>Lachnospiraceae *↓<br>Roseburia ↓<br>Faecalibacterium ↓<br>Ruminococcus ↓<br>Erysipelotrichaceae *↓ | Succinivibrio ↑ | | | Treponema ↑ | ↑ | [53, 55] | | High-fat and animal protein diet (Western dietterm) | Actinobacteriaterm *↑ | Bacteroidesterm ↑<br>Alistipes ↑<br>Barnesiella ↑ | Roseburia ↓<br>Eubacterium rectale ↓<br>Ruminococcus bromii ↓ | Bilophila ↑ | | | | ↓ | \* Unknown genera. (1) Main genera.
2.2.1. Enterotypesterm Gut microbiotaterm of each individual are specifically characterized by clusters of bacteria named enterotypesterm [13]. Three enterotypesterm are characterized by three dominant bacteria clusters ( Table 2): Bacteroidesterm (enterotype Iterm), Prevotellaterm (enterotype IIterm), or Ruminococcus (enterotype IIIterm). Each enterotypeterm harbors different bacteria genera ( Table 1). These three enterotypesterm are not only enumerations of bacteria; they are also specifically regrouped by functions. Indeed, an enterotype isterm a functional harmonious association of several bacteria speciesterm rather than a systematic addition of bacteria speciesterm. Every enterotype isterm not a clear-cut identity such as blood groupsterm; however, enterotypesterm characterize individuals, remain stable from adulthood, and can be restored if they are modified. Each enterotypeterm with its distinctive clusters of bacteria and respective functional characteristics defines a distinctive way of generating energy from fermentable substratesterm available in the colon. Indeed, bacteria clusters of enterotype Iterm derive energy primarily from carbohydrates using principally glycolysis and pentose phosphate pathwaysterm, whereas bacteria clusters of enterotypesterm II and III are able to degrade mucin glycoproteinsterm of the gutterm mucosal layer. Enterotypesterm seem to be principally defined according to dietary habitsterm. Understanding the origins and functions of enterotypesterm may improve the knowledge of the relationships between gut microbiotaterm and human health.
2.2.2. Body Mass Index (BMI) Classes Several studies [50, 51] have examined the impact of childhood BMI on gut microbiotaterm composition and demonstrated that children with overweight or normal BMI are provided with a higher microbial diversityterm than underweight children. Gut microbiotaterm diversityterm descends stepwise based on BMI class [50, 52].
Bervoets et al. [53] demonstrated that the microbiota of obese children are provided with an elevated Firmicutes-to-Bacteroidetes ratioterm compared to the microbiota of lean children [53]. Furthermore, low relative proportions of Bifidobacteriumterm vulgatus and high concentrations of Lactobacillus spp. are observed in the obese microbiota [53]. Riva et al. [54] confirmed that obesity is associated with elevated levels of Firmicutesterm such as Ruminococcaceae and depleted levels of Bacteroidetesterm such as Bacteroidaceae and Bacteroidesterm. SCFAsterm are higher in obese children suggesting elevated substrate utilization. These findings suggest that the dysbiosisterm of gut microbiotaterm may contribute to the pathophysiology of obesity and the increased ratio of Firmicutesterm to Bacteroidetesterm is associated with the increased production of SCFAsterm and energy harvest from colonic fermentationterm [54].
The underweight BMI levelterm also revealed profound gut microbiotaterm variations. Borgo et al. [55] performed a comprehensive data analysis comparing gut microbiotaterm and anthropometric traits of 15 anorexia nervosa (AN)term women and healthy controls. Results showed that AN intestinal microbiota showed a significant increase in Enterobacteriaceaeterm and Methanobrevibacter smithii compared with healthy controls [55]. On the contrary, the genera Roseburia, Ruminococcus, and Clostridiumterm were depleted in line with the observed reduction in AN of the total SCFAsterm [55].
BMI levelsterm represent a valid predictive value for gut microbiota dysbiosisterm. Studies have demonstrated that gut microbiotaterm variations are correlated with increased or depleted production of SCFAsterm that may respectively contribute to the pathophysiology of obesity or AN. Interventions such as prebiotics and probioticsterm may be possible solutions to manage both pediatric obesity [50] and AN patients.
2.2.3. Ethnicity, Dietary Habitsterm, and Cultural Habits While the microbiome of a healthy individual is relatively stable, gutterm microbial dynamics can certainly be influenced by lifestyle and dietary cultural choices [56]. A study of European children (fed with the Western dietterm) and Burkina Faso children (assuming a diet rich in millet/sorghum + local vegetables containing very few lipids and animal proteins) [57] revealed that African children’s microbiota have a remarkable abundance of Prevotellaterm and Xylanibacter. Furthermore, Shigella and Escherichia are widely under-represented. Another study [58] compared Hadza hunter-gatherers and Italian gut microbiotaterm. At the phylum level, Hadza gut microbiotaterm are largely enriched in Proteobacteriaterm and Spirochaetes, which are extremely rare in the Italian gut microbiotaterm, whereas Actinobacteriaterm, an important subdominant component of the Italian gut microbiotaterm, are almost absent. At the genus level, Hadza gut microbiotaterm are comparatively enriched in Prevotellaterm, Eubacterium, Oscillibacter, Butyricicoccus, Sporobacter, Succinivibrio, and Treponema and correspondingly depleted in Bifidobacteriumterm, Bacteroidesterm, Blautia, Dorea, unclassified Lachnospiraceae, Roseburia, Faecalibacterium, Ruminococcus, and unclassified Erysipelotrichaceae. These two studies showed that African gut microbiotaterm have clearly an enterotypeterm Prevotellaterm (enterotype IIterm); the African dietterm rich in millet/sorghum + local vegetables containing very few lipids and animal proteins allows a mucine degradation in synergy with Desulfovibrionaceae. European gut microbiotaterm (Western dietterm) have principally an enterotypeterm Bacteroidesterm (enterotype Iterm): the European diet rich in lipids and animal proteins allows energy production from carbohydrates and proteins through fermentation [13]. David et al. [59] compared plant-based diet microbiometerm (high fibers and low fats and proteins) with animal-based diet microbiometerm (low fibers and high fats and proteins) and respective changes in microbiome on either diet and demonstrated that a shift toward an animal-based diet increases the abundance of bile-tolerant microorganismsterm ( Alistipes, Bilophila, and Bacteroidesterm) and decreases the levels of Firmicutesterm that metabolize dietary plant polysaccharides ( Roseburia, Eubacterium rectale, and Ruminococcus bromii). Moreover, microbial activity trades off between carbohydrate and protein fermentationterm when the type of diet respectively changes. This change occurred only one day after the diet reached the distal gut microbiotaterm. David et al. [59] showed that diet alters human microbiota rapidly and reproducibly.
2.2.4. Exercise Frequency Bai et al. [50] suggested associations of exercise frequency with gut microbiotaterm composition of young children and adolescents. Daily exerciseterm increases gut microbial diversityterm ( Table 2) with a Firmicutesterm enrichment microbiota: Clostridiales, Roseburia, Lachnospiraceae, and Erysipelotrichaceae by producing more SCFAsterm which may increase the expression of tight junction proteinsterm in colon epithelia to heighten the resistance of the intestinal barrier, reduce mucosal permeabilityterm, and inhibit inflammatory cytokinesterm [50, 60].
Clarke et al. [61] explored exercise and protein consumption for their impact on the gut microbiotaterm of professional athletes from an international rugby union squad. A higher alpha diversityterm of gutterm microorganisms representing more than 20 distinct phyla has been demonstrated in athletes compared with high and low BMI controls [61]. Indeed, this study showed that exercise increases gut microbial diversityterm ( Table 2) and protein consumption positively correlates with microbial diversityterm. These results provide evidence for a beneficial impact of exercise on gut microbiotaterm diversityterm, but also indicate that the relationship exercise–microbiota diversityterm is probably related to accompanying dietary extremes [61].
3. Gut Microbiotaterm Variations in Health and Diseaseterm Gut microbiotaterm composition is highly variable. The variation itself is considered as physiological in the context of healthy gut microbiotaterm, according to age, ethnicity, lifestyle, and dietary habitsterm. However, these physiological gut microbiota variationsterm have huge implications in intestinal and extra-intestinal disordersterm. Indeed, dysbiosisterm is often defined as an alteration of gut microbiota compositionterm and a cause or a consequence of disorders. It is often difficult to ascertain whether the change is beneficial or detrimental. As for the human conditions, changes represent a challenge for a better adaptation in a new context and may potentiate resilience. However, a chronic external stimulationterm may be stressful and disruptive for an unstructured ecosystemterm. We will discuss the correlations between several diseasesterm and alterations of gut microbiotaterm composition.
3.1. Intestinal Disorders 3.1.1. Irritable Bowel Syndrome Irritable bowel syndrome (IBS)term is one of the most common gastrointestinal (GI) disorders and the bacterial role has been largely investigated [62].
The study [63] of fecal and colonic mucosal biopsy samples from IBS patients and healthy controls demonstrated a significant reduction in the concentration of aerobic bacteria such as the Lactobacillus species in fecal samples from IBS patients compared to healthy controls. Another study [64] demonstrated that the microbial communities of IBS patients are enriched in Proteobacteriaterm and Firmicutesterm but reduced in Actinobacteriaterm and Bacteroidetesterm compared to controls. In particular, 16S rDNA sequences belonging to the family Lachnospiraceae within the phylum Firmicutesterm are in greater abundance in the IBS clone library [64].
Other studies [62, 65] confirmed and revealed some phyla and genera variations in IBS patients compared to healthy controls: an increase in the Firmicutes-to Bacteroidetes-ratio, a decrease in some Firmicutesterm families ( Lactobacilli, Faecalibacterium) and the Actinobacteriaterm population (Bifidobacteria, Collinsella), and an increase in some Firmicutesterm families ( Veillonella, Streptococci, and Ruminococcus spp.) and in Proteobacteriaterm ( Enterobacteriaceaeterm spp.). Therefore, these findings demonstrated a loss of microbial richnessterm that may be involved in amino acid synthesis, in the integrity of cellular junctions, and in inflammatory response, suggesting a weakness of the epithelial barrier functionsterm partially explaining IBS symptoms.
3.1.2. Inflammatory Bowel Diseaseterm (IBD) Inflammatory bowel diseases (IBD)term gather idiopathic, chronic, and relapsing inflammatory conditions of the gastrointestinal tract including ulcerative colitis (UC)term and Crohn’s disease (CRD)term.
The findings of Frank et al. [66] indicated a diminution of Lachnospiraceae and Bacteroidetesterm microbial populations and an increase in Proteobacteriaterm families in IBD patients compared to control gut microbiotaterm.
Gut microbiotaterm variations appear to be different between UC and CRD. Indeed, a decreased abundance of the butyrate-producing bacteriaterm Roseburia hominis and Faecalibacterium prausnitziiterm has been observed in UC patients relative to controls [67], whereas the opposite has been observed in CRD patients, who are provided with increased Faecalibacterium prausnitziiterm levels in addition to a reduced overall diversityterm [68].
In the case of CRD patients, another study [69] demonstrated a decrease in Dialister invisus, an uncharacterized species of Clostridiumterm spp., in Faecalibacterium prausnitziiterm, and in Bifidobacteriumterm adolescentis and an increase in Ruminococcus gnavus.
Sokol et al. [70] confirmed the reduction of F. prausnitzii in CRD patients and also demonstrated that an oral administrationterm of live Faecalibacterium prausnitziiterm reduced the severity of colitisterm and tended to correct the dysbiosisterm. These results suggest that counterbalancing dysbiosisterm using Faecalibacterium prausnitziiterm as a probiotic is a promising strategy in CRD treatment [70].
These results do not demonstrate a causal relationship between microbial dysbiosisterm and IBD pathophysiology, but they rather suggest that gutterm microbial unbalances are likely to contribute to diseaseterm severity.
3.1.3. Celiac Diseaseterm Celiac disease (CD)term is a chronic intestinal inflammatory disorder due to an aberrant immune responseterm to dietary gluten proteins in genetically predisposed individuals.
Gut microbiotaterm variations may play a significant role in the pathogenesis of CD; indeed, dysbiosisterm is linked with an inflammatory milieu in celiac patients [71]. Celiac diseaseterm is caused by the interplay between gluten, genetic factors, and environmental factorsterm such as gut microbiotaterm [72].
Studies [73, 74, 75, 76] have demonstrated that Bifidobacteriumterm spp., Bifidobacteriumterm longum, Clostridiumterm histolyticum, C. lituseburense, and Faecalibacterium prausnitziiterm group proportions are less abundant in untreated CD patients than in healthy controls. Indeed, patients with CD show a reduction in beneficial species ( Lactobacillus and Bifidobacteriumterm) and an increase in those potentially pathogenic ( Bacteroidesterm and E. coli) as compared to healthy subjects [74]. The mucosal layer of CD patients fails to stabilize the gut microbiotaterm and fails to prevent the host from the invasion of harmful antigens and pathogens [71]. This dysbiosisterm is reduced, but may still remain, after a gluten-free dietterm [71, 73].
3.1.4. Colorectal Cancerterm (CRC) Colorectal cancerterm is the third most common cause of cancer mortality in the world [77]. Structural fecal bacterial segregations between CRC patients and healthy volunteers have been demonstrated [78]. The gut microbiotaterm of the CRC patients were enriched in Bacteroidesterm fragilis, Enterococcus, Escherichia/Shigella, Klebsiella, Streptococcus, and Peptostreptococcus and were impoverished in Roseburia and other butyrate-producing bacteriaterm of the family Lachnospiraceae [78]. The gut microbiotaterm of the healthy volunteers were enriched in Bacteroidesterm vulgatus and Bacteroidesterm uniformis. Therefore, gut microbiotaterm variations, such as a reduction of butyrate producers and an increase in opportunistic pathogensterm, constitute a major structural imbalance of gut microbiotaterm in CRC patients.
Shen et al. [79] demonstrated a higher abundance of Proteobacteriaterm and a lower abundance of Bacteroidetesterm in CRC cases compared to controls. At the genus level, CRC cases showed an increased abundance of Dorea spp. and Faecalibacterium spp. and lower proportions of Bacteroidesterm spp. and Coprococcus spp. than controls.
Genomic analysis identified an association of Fusobacteriumterm spp. with colorectal cancerterm [80]; the microbiota of CRC patients were enriched in Fusobacteriumterm spp., whereas the Bacteroidetesterm and Firmicutesterm phyla were depleted. Furthermore, Fusobacteriumterm spp. may contribute to tumorigenesis by an inflammatory-mediated mechanismterm [80], but the precise role of Fusobacteriaterm in colorectal carcinoma pathogenesis requires further investigation.
All these findings reveal alterations in CRC microbiota that may contribute to the etiology of colorectal cancerterm. The extension of these findings may lead to strategies able to manipulate microbiota to prevent colorectal cancerterm as well as to identify individuals at high risk [79].
3.2. Extra-Intestinal Disorders We highlighted that the pivotal relationship between gut microbiotaterm and the host is involved in many intestinal disorders. Recent advances in research have demonstrated that this mutualistic gut microbiotaterm–host relationship appears to play a critical role for many extra-intestinal diseasesterm such as metabolic diseasesterm and neurological disorders with “gut–brain axisterm” interactions [81], but also for complex multifactorial diseasesterm such as age-related macular degeneration with “gut–retina axisterm” interactions [82].
3.2.1. Metabolic Disorders ##### Obesity Animal studies constitute the majority of causative evidence linking changes in microbial composition to obesity while, in humans, data are more variable. In addition, although the majority of mouse gutterm species are unique, the mouse and human microbiota are similar at the division level, with Firmicutesterm and Bacteroidetesterm dominating [83].
The analysis [83] of gut microbiotaterm of genetically obese ob/ob mice and lean mice all fed the same polysaccharide-rich diet revealed a lower relative abundance (50%) of Bacteroidetesterm in obese ob/ob mice, whereas the Firmicutesterm are correspondingly higher. Indeed, higher numbers of Ruminococcaceae and Rikenellaceae have been observed in leptin-resistant obese (leptin-promoting satiety) and diabetic mice (db/db) compared with their lean littermates [84]. In addition, the higher abundance of Ruminococcaceae and Rikenellaceae in mice fed a high-fat diet is not only dependent on the ingested diet but is also closely linked with obesity and type 2 diabetesterm [85]. Furthermore, the association between Desulfovibrionaceae abundance and obesity and type 2 diabetesterm has been demonstrated [86, 87]. Other studies [50, 88] confirmed the role of Proteobacteriaterm in obesity by producing pro-inflammatory molecules such as lipopolysaccharidesterm and helping to harvest energy and increase host fat storageterm [88].
On the contrary, researchers [86, 89] have recently demonstrated that Akkermansia muciniphilaterm, a mucin-degrading bacteria living in the mucus layer [90], decreases in both genetically and diet-induced obese mice.
All these studies highlight the finding that obesity is associated with changes in the composition of gut microbiotaterm including lower species diversityterm and shifts in the abundance of genes involved in metabolism. These gut microbiotaterm variations affect the microbiome which has an increased capacity to harvest energy from the dietterm and these changes are transmissible [91]. Gut microbiotaterm can be considered as a contributing factor to the pathophysiology of obesity and may have potential therapeutic implications.
##### Type 2 Diabetesterm (T2D) Several studies [92, 93] demonstrated that gut microbiotaterm composition is altered in patients suffering from T2D, but it is not clear whether these changes are a cause or simply a consequence of the disorder.
Larsen et al. [92] showed that the proportions of phyla Firmicutesterm and Clostridia are significantly reduced in the T2D sufferers compared to the healthy group. Furthermore, the ratios of Bacteroidetesterm to Firmicutesterm, the ratios of Bacteroides-Prevotella, and Betaproteobacteria are highly increased in T2D sufferers compared to healthy patients and positively correlated with plasma glucose.
A metagenome-wide association study of gut microbiotaterm of T2D Chinese sufferers [94] demonstrated that patients with type 2 diabetesterm were characterized by a decrease in butyrate-producing bacteriaterm such as Roseburia spp. and an increase in various opportunistic pathogensterm ( Clostridiumterm spp., Bacteroidesterm caccae) as well as an enrichment of other microbial functions conferring sulfate reduction ( Desulfovibrionaceae spp.).
Gut microbiotaterm interact with various host sensing and signaling pathwaysterm, leading to a modulation of the endocrine systemterm, immune responsesterm, nervous system activityterm, and hence, the predisposition to metabolic diseasesterm. Gut microbiota dysbiosisterm drives and implies new therapeutic strategies for diabetes and related metabolic diseasesterm [95].
3.2.2. Central Nervous Systemterm (CNS)-Related Disorders The brainterm and the gutterm are connected via the gut–brain axisterm with bidirectional interactionsterm between the central nervous systemterm, the enteric nervous systemterm, and the gastrointestinal tract. These bidirectional interactionsterm enable the brainterm to influence gastrointestinal functions as well as immune functions.
##### Alzheimer’s and Parkinson’s Diseasesterm Today, over 46 million people live with dementia worldwide [96]. Alzheimer’s disease (AD)term and Parkinson’s disease (PD)term are considered the most common forms of dementia in the elderly.
Alzheimer’s disease (AD)term is a chronic, rapidly progressive neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-beta peptidesterm. Cattaneo et al. [97] demonstrated that an increase in Escherichia/Shigella abundance and a reduction of E. rectale abundance are possibly associated with a peripheral inflammatory state in patients with cognitive impairmentterm and brainterm amyloidosis. Vogt et al. [98] compared gut microbiotaterm composition from patients with and without a diagnosis of AD and revealed a lower microbial diversityterm compositionally distinct from control-age and sex-matched individuals, with a decrease in Firmicutesterm and Bifidobacteriumterm abundance and an increase in Bacteroidetesterm abundance in the microbiome of AD participants.
The gut microbiotaterm variations are also involved in the pathogenesis of PD. Hopfner et al. [99] suggested, in agreement with most other studies [100, 101, 102], an increase in Lactobacillaceae abundance in Parkinson patients compared to healthy controls. Moreover, none of the differences in alpha diversityterm has been observed between PD cases and controls, whereas beta diversityterm has been revealed for three bacterial families ( Lactobacillaceae, Barnesiellaceae, and Enterococcaceae) [99]. PD is associated with changes in gut microbiotaterm and this gut microbiota dysbiosisterm may be the mechanism of neuroinflammationterm that leads to PD pathologyterm [99].
##### Hepatic Encephalopathy Hepatic encephalopathy (HE)term is a complication of cirrhosis and is defined as a spectrum of neuropsychiatric abnormalities in patients with liver dysfunctions. Bajaj et al. [103] linked the gut microbiotaterm composition with cognition and inflammation in HE. Fecal microbiota of cirrhotics were significantly higher in Enterobacteriaceaeterm, Alcaligenaceae, and Fusobacteriaceae and lower in Ruminococcaceae and Lachnospiraceae compared with controls [103]; moreover, altered higher levels of Veillonellaceae were found in HE patients compared with cirrhotics without HE. In the cirrhosis group, Alcaligenaceae and Porphyromonadaceae were positively correlated with cognitive impairmentterm. Fusobacteriaceae, Veillonellaceae, and Enterobacteriaceaeterm were positively and Ruminococcaceae was negatively related to inflammation. Thus, cirrhosis, especially when complicated with HE, is associated with significant gut microbiotaterm alterations compared with healthy individuals. Specific bacterial families ( Alcaligenaceae, Porphyromonadaceae, and Enterobacteriaceaeterm) are strongly associated with cognition and inflammation in HE [103].
##### Autism Spectrum Disordersterm Compared with the gut microbiotaterm of children without ASD, the gut microbiotaterm of children with ASD is less diverse and exhibits lower levels of Bifidobacteriumterm and Firmicutesterm and higher levels of Lactobacillus, Clostridiumterm, Bacteroidetesterm, Desulfovibrio, Caloramator, and Sarcina [104, 105, 106, 107]. A study by Wang et al. [108] showed a decrease in Bifidobacteriumterm spp. and mucolytic bacteria Akkermansia muciniphilaterm in the gut microbiotaterm of autism subjects compared to control subjects.
Williams et al. [109] found an increase in the Firmicutes-to-Bacteroidetes ratioterm and a significant increase in Sutterella compared to their abundance in controls. These findings demonstrated that gut microbiota dysbiosisterm has close relationships with gastrointestinal and behavioral manifestations of autismterm.
##### Stress The bidirectional interactionsterm of gutterm–brainterm mean that the brainterm can also alter gut microbiotaterm composition [110]. A model of social disruption among adult mice [111] demonstrated that exposure to stressterm results in substantial changes in gut microbiota compositionterm: a decrease in Bacteroidesterm spp. abundance and an increase in Clostridiumterm spp. abundance have been observed in stress-induced mice relative to controls. The mechanisms by which stress influences gut microbiotaterm composition are unclear but include microbial habitat alterations following stress-induced changes in intestinal mobilityterm and mucin secretionterm [110, 112].
Other studies [62] revealed that chronic psychological stress is reflected in the microbiota composition. Indeed, depression due to chronic stressful life events is associated with an increase in Enterobacteriaceaeterm, whereas psychological stress is associated with a reduction in Lactobacilli spp. and an increase in Escherichia coli and Pseudomonas spp.
Gut microbiotaterm variations are closely associated with the onset of these neurological disorders, and the gut bacterial communitiesterm may be a target for therapeutic interventionsterm.
4. Conclusions Each healthy human is provided with unique gut microbiotaterm. Core native microbiota are shaped in early life (4–36 months) by gutterm maturation developing from enterotypeterm, birth gestational ageterm, type of deliveryterm·var, methods of milk feeding, weaning period, lifestyle, and dietary and cultural habits. After a child reaches 2–3 years old, a relative stability in gut microbiotaterm composition has been demonstrated. Richness and diversityterm of gut microbiotaterm shaped in early life characterize a healthy gut microbiotaterm composition. However, this optimal healthy gut microbiotaterm composition is different for each individual.
Throughout life, the richer and more diverse the microbiota, the better they will withstand external threats. Indeed, gut microbiotaterm represent a changing ecosystem that is severely tested by many factors such as unbalanced diet, stress, antibiotic use, or diseasesterm. A healthy host–microorganism balanceterm must be respected in order to optimally perform metabolic and immune functionsterm and prevent diseaseterm development. Indeed, disturbances to the delicate host–microbe relationshipterm may disrupt the development of the immune system, which may in turn result in diseasesterm [113]. Although the role of gut microbiotaterm is still poorly understood, the close association between gut microbiota dysbiosisterm and intestinal and extra-intestinal disordersterm has been demonstrated. This is the reason why dysbiosisterm can be considered as a biomarkerterm of such disorders and that the study of gut microbiotaterm balances shall be one of the priorities for future therapiesterm to prevent and treat diseasesterm.
Author Contributions Conceptualization, E.R. and M.C.M.; Data Research, M.C.; Data Curation, M.C.; Writing—Original Draft Preparation, P.R.; Writing—Reviewterm·mth & Editing, E.R. and M.C.M.; Visualization, G.A.D.M.; Supervision, F.F. and A.G.
Funding This research received no external funding.
Conflicts of Interest The authors declare no conflict of interest.