Interaction between microbiota and immunity in health and disease

Interaction between microbiota and immunity in health and disease Danping Zheng Timur Liwinski Eran Elinav

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Interaction between microbiota and immunity in health and disease 2020 Cell Research 10.1038/s41422-020-0332-7 zheng2020-interaction-between-microbiota-and zheng2020-interaction-between-microbiota-and.txt, the project's staged copy 93a32619ca8aab6669db47c6650d87e747eb3434 cc-by biology

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0 spans located by searching the stored text for the quote's exact words, allowing any whitespace between them the two-way traffic between the commensal microbiota and the mammalian immune system - how microbes train immunity and how immunity in turn shapes which microbes persist Quotation withheld because this record is not cleared for redistribution. which microbiome-immunity interactions are mechanistically established, and what still stands between association and a causal claim in human disease Quotation withheld because this record is not cleared for redistribution. a review that organises the mechanisms by compartment and by disease and then states plainly that a direct causal relationship has not been established in most medical conditions - the negative claim is the contribution Quotation withheld because this record is not cleared for redistribution. critique Quotation withheld because this record is not cleared for redistribution. host-microbe mutualism and its breakdown - a relationship in which each side regulates the other, so that neither perturbation nor dysregulation can be read as the cause of the other from observation alone Quotation withheld because this record is not cleared for redistribution. review review Quotation withheld because this record is not cleared for redistribution. the causal claims of this field rest on germ-free animals - raised with no commensals at all. That is the cleanest possible contrast and it is also a state no animal is ever in outside a facility, so what it establishes is that commensals matter, not which ones do what at natural abundance an instrument that is an extreme, not a control Quotation withheld because this record is not cleared for redistribution. microbiota drive immune activation and inflammation conversely reshapes the microbial community. When each side changes the other, an observed association in a diseased human carries no direction, which is exactly why the authors say the causal relationship before onset has not been established bidirectionality defeats observation Quotation withheld because this record is not cleared for redistribution. 16S rRNA sequencing reports genus and composition. Every strain-level and every functional difference in the reviewed literature was therefore not measured rather than not present - and the recommendation to move to shotgun metagenomics is a statement about what the existing corpus of findings could not have seen the resolution decides the finding Quotation withheld because this record is not cleared for redistribution. NLRP6's effect on microbiota structure appears only where the background microbiota contains particular pathobionts such as Helicobacter. A knockout phenotype that depends on the vivarium is a joint property of gene and facility, and two labs reporting different results may both be right the phenotype belongs partly to the building Quotation withheld because this record is not cleared for redistribution. faecal microbiome transplantation aims to restore a healthy microbiome configuration, and the authors state there is no general consensus on which features constitute a healthy microbiome. The therapy is specified by its mechanism and not by its endpoint a target with no definition Quotation withheld because this record is not cleared for redistribution. a direct causal relationship between the microbiome and immunity before onset or in early disease has not been established in most medical conditions Quotation withheld because this record is not cleared for redistribution. the causal effect of the microbiome on immune dysregulation in most human disorders remains to be proven Quotation withheld because this record is not cleared for redistribution. the field runs on laboratory mice whose microbiota is divergent from wild animals and humans, limiting translational potential and reproducibility Quotation withheld because this record is not cleared for redistribution. most of the reviewed work used 16S rRNA sequencing, which resolves genus and composition only and cannot see strain-level or functional differences Quotation withheld because this record is not cleared for redistribution. inter-individual variation typically explains more variance in both microbiome and immune response than disease state does Quotation withheld because this record is not cleared for redistribution. there is no general consensus on which features constitute a healthy microbiome, so FMT efficacy in IBD remains under evaluation Quotation withheld because this record is not cleared for redistribution. the prophylactic and therapeutic efficacy of traditional individual probiotics in promoting human health is limited about this quote: PAGE FURNITURE IS SPLICED INTO THE 'evidence' QUOTE - the journal's running head and a page number, 'Review Article 501 Cell Research…', between 'potentially' and 'may provide'. The words on either side of it were never continuous on the page; read the quote with it deleted. Quotation withheld because this record is not cleared for redistribution. the review does not claim coverage - it states that the evidence cannot be summarised in one review and refers out to others Quotation withheld because this record is not cleared for redistribution. machine learning, proposed for decoding individualised microbiome patterns - a response to inter-individual variance being larger than the disease signal Quotation withheld because this record is not cleared for redistribution. shotgun metagenomic sequencing and the wider multi-omics stack, carried from genomics into immunology to replace a genus-level instrument Quotation withheld because this record is not cleared for redistribution. germ-free animals, raised with no commensal microbes at all, used as the reference state for every claim that a commensal is required for an immune structure eliminates: the possibility that the lymphoid and immune defects are produced by something other than the absence of commensals - there are none to confound with · outcome: held Quotation withheld because this record is not cleared for redistribution. Th17 cells scored in germ-free mice and again after defined colonisation, with SFB and with other commensals separately eliminates: the Th17 population being a fixed host trait - it is absent without microbes and returns on colonisation, so the microbe is doing the work · outcome: held Quotation withheld because this record is not cleared for redistribution. laboratory mice given a wild microbiota, then challenged with influenza virus and with colitis-induced tumorigenesis eliminates: the host genotype explaining the difference - the same laboratory animal changes phenotype when only the microbiota is swapped · outcome: held Quotation withheld because this record is not cleared for redistribution. microbiome depletion by broad-spectrum antibiotics in humans, followed by seasonal influenza vaccination and plasma metabolome profiling eliminates: reverse causation from immune state to microbiome - here the microbiome was depleted deliberately and the antibody response followed · outcome: held Quotation withheld because this record is not cleared for redistribution. NLRP6-deficient mice compared across vivaria with different background microbiota, rather than in one facility eliminates: a gene effect that is really a facility effect - and the comparison shows the phenotype appears ONLY where particular pathobionts are present · outcome: partial Quotation withheld because this record is not cleared for redistribution. integration of multi-omics data sets - metagenomics, single-cell transcriptomics, epigenomics, proteomics and metabolomics - proposed for disentangling the interaction under host genetics and environmental triggers eliminates: the direction of the microbiota-immune relationship, which the cited animal evidence shows to be bidirectional - the multi-omics integration that would separate cause from consequence is proposed, not done · outcome (stated by the tagger, no quotation): absent-declared-unreported Quotation withheld because this record is not cleared for redistribution. faecal microbiome transplantation in IBD, named as under evaluation with fecal processing and patient safety unresolved eliminates: whether restoring the microbiome restores the immune phenotype - named as under evaluation, with faecal processing and patient safety unresolved · outcome (stated by the tagger, no quotation): absent-declared-unreported Quotation withheld because this record is not cleared for redistribution. microbiome microbiome Quotation withheld because this record is not cleared for redistribution. germ-free germ-free Quotation withheld because this record is not cleared for redistribution. segmented filamentous bacteria segmented filamentous bacteria Quotation withheld because this record is not cleared for redistribution. Th17 Th17 Quotation withheld because this record is not cleared for redistribution. Broad-spectrum antibiotic Broad-spectrum antibiotic Quotation withheld because this record is not cleared for redistribution. SCFAs SCFAs Quotation withheld because this record is not cleared for redistribution. 16S rRNA sequencing 16S rRNA sequencing Quotation withheld because this record is not cleared for redistribution. shotgun metagenomic sequencing shotgun metagenomic sequencing Quotation withheld because this record is not cleared for redistribution. laboratory mice laboratory mice Quotation withheld because this record is not cleared for redistribution. wild mice wild mice Quotation withheld because this record is not cleared for redistribution. inter-individual variation inter-individual variation Quotation withheld because this record is not cleared for redistribution. disease state disease state Quotation withheld because this record is not cleared for redistribution. Bilophila wadsworthia Bilophila wadsworthia Quotation withheld because this record is not cleared for redistribution. NLRP6 NLRP6 Quotation withheld because this record is not cleared for redistribution. humans humans Quotation withheld because this record is not cleared for redistribution. colitis colitis Quotation withheld because this record is not cleared for redistribution. vivarium vivarium Quotation withheld because this record is not cleared for redistribution. the microbiome-immunity relationship - AS ESTABLISHED: a bidirectional relationship in animal models, where microbiota drive immune activation and inflammation conversely reshapes the community Quotation withheld because this record is not cleared for redistribution. the microbiome-immunity relationship - AS NOT ESTABLISHED: a direct causal relationship before onset or in early disease, which the authors say has not been shown in most medical conditions Quotation withheld because this record is not cleared for redistribution. the microbiome - AS MEASURED BY 16S rRNA SEQUENCING: genus-level and purely compositional, which is the resolution most of the literature reviewed here was produced at Quotation withheld because this record is not cleared for redistribution. the microbiome - AS MEASURED BY SHOTGUN METAGENOMICS: strain-level and functional, the resolution the authors say the field must move to Quotation withheld because this record is not cleared for redistribution. a 'healthy' microbiome - AS A THERAPEUTIC TARGET: the configuration FMT aims to restore, and on which the authors say there is still no general consensus Quotation withheld because this record is not cleared for redistribution. the mouse microbiota - IN THE LABORATORY: divergent from wild animals and humans, with limited translational potential Quotation withheld because this record is not cleared for redistribution. the mouse microbiota - IN THE WILD: resilient, and shown to recapitulate human phenotypes better - laboratory mice receiving it become less susceptible to influenza and to colitis-induced tumorigenesis Quotation withheld because this record is not cleared for redistribution. qualifies → its own field's causal language about the microbiome, by stating that a direct causal relationship has not been established in most medical conditions Quotation withheld because this record is not cleared for redistribution. critiques → the reliance on laboratory mice, whose microbiota is divergent from wild animals and humans and whose translational potential is therefore limited Quotation withheld because this record is not cleared for redistribution. critiques → 16S rRNA sequencing as the field's default instrument, on the grounds that its genus-level compositional resolution cannot register strain or function Quotation withheld because this record is not cleared for redistribution. qualifies → microbiome-targeted therapy, by noting that there is no consensus definition of the healthy configuration such therapy aims to restore Quotation withheld because this record is not cleared for redistribution. builds-on → germ-free and gnotobiotic animal work as the basis for every mechanistic claim in the review Quotation withheld because this record is not cleared for redistribution. laboratory mice —distinct-from→ humans laboratory mice humans differs in: whether the microbiota is the one the conclusion is meant to be about · the relation itself is separately evidenced · strength of the relation: 0.95 · differs in (stated by the tagger, no quotation): whether the microbiota is the one the conclusion is meant to be about · the relation stated: nearly all of this evidence comes from mice carrying a microbiota the authors call divergent from wild animals and from humans, which bounds what any of it translates to Audit 2026-09-28: DOUBTFUL - read against its span and kept, but laboratory mice carry a divergent microbiota; distinct-from is loose. Quotation withheld because this record is not cleared for redistribution. inter-individual variation —distinct-from→ disease state inter-individual variation disease state differs in: which source of variance a case-control comparison is actually measuring · the relation itself is separately evidenced · strength of the relation: 0.95 · differs in (stated by the tagger, no quotation): which source of variance a case-control comparison is actually measuring · the relation stated: in both microbiome configuration and immune response, more variance is typically explained by who the person is than by whether they are ill Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span says more variance is explained by inter-individual variation than by disease state; distinct-from is loose. Quotation withheld because this record is not cleared for redistribution. segmented filamentous bacteria —causes→ Th17 segmented filamentous bacteria Th17 direction on the measure: increases · the relation itself is separately evidenced · strength of the relation: 0.95 · direction on the measure (stated by the tagger, no quotation): increases · the relation stated: Th17 cells are absent in germ-free mice and are induced by colonisation, most notably with SFB - a single named commensal producing a defined immune cell population Quotation withheld because this record is not cleared for redistribution. Broad-spectrum antibiotic —causes→ SCFAs Broad-spectrum antibiotic SCFAs direction on the measure: reduces · the relation itself is separately evidenced · strength of the relation: 0.95 · direction on the measure (stated by the tagger, no quotation): reduces · the relation stated: broad-spectrum antibiotics perturb the microbiota and deplete microbiota-derived SCFAs, and that depletion hyperactivates intestinal macrophages, expands pro-inflammatory T helper cells and raises susceptibility to infection Quotation withheld because this record is not cleared for redistribution. Bilophila wadsworthia —causes→ colitis Bilophila wadsworthia colitis direction on the measure: increases · the relation itself is separately evidenced · strength of the relation: 0.95 · direction on the measure (stated by the tagger, no quotation): increases · the relation stated: saturated fat raises taurocholic acid, which expands this pathobiont, which promotes Th1 responses and raises colitis susceptibility - the review's most completely specified dietary chain Quotation withheld because this record is not cleared for redistribution. a direct causal relationship between microbiome and immunity before disease onset has not been established in most medical conditions a direct causal relationship between microbiome and immunity before disease onset has not been established in most medical conditions Quotation withheld because this record is not cleared for redistribution. Th17 cells are absent in germ-free mice and are induced by colonisation, most notably with segmented filamentous bacteria Th17 cells are absent in germ-free mice and are induced by colonisation, most notably with segmented filamentous bacteria Quotation withheld because this record is not cleared for redistribution. broad-spectrum antibiotics deplete microbiota-derived SCFAs, hyperactivating intestinal macrophages and increasing susceptibility to infection broad-spectrum antibiotics deplete microbiota-derived SCFAs, hyperactivating intestinal macrophages and increasing susceptibility to infection Quotation withheld because this record is not cleared for redistribution. microbiome depletion by antibiotics diminishes the antibody response to seasonal influenza vaccination in humans microbiome depletion by antibiotics diminishes the antibody response to seasonal influenza vaccination in humans Quotation withheld because this record is not cleared for redistribution. a diet high in saturated fats raises taurocholic acid, expands Bilophila wadsworthia and increases colitis susceptibility a diet high in saturated fats raises taurocholic acid, expands Bilophila wadsworthia and increases colitis susceptibility Quotation withheld because this record is not cleared for redistribution. NLRP6's effect on microbiota structure appears only against a background microbiota containing particular pathobionts, so the phenotype depends on the vivarium NLRP6's effect on microbiota structure appears only against a background microbiota containing particular pathobionts, so the phenotype depends on the vivarium Quotation withheld because this record is not cleared for redistribution. more variance in microbiome configuration and immune response is explained by inter-individual variation than by disease state more variance in microbiome configuration and immune response is explained by inter-individual variation than by disease state Quotation withheld because this record is not cleared for redistribution. there is no general consensus on which features constitute a healthy microbiome there is no general consensus on which features constitute a healthy microbiome Quotation withheld because this record is not cleared for redistribution. an animal model raised without commensal microbes, used as the field's instrument for mechanistic causal relationships between microbiota and host immunity germ-free Quotation withheld because this record is not cleared for redistribution. a modality limited to genus-level and purely compositional resolution, as against shotgun metagenomics which resolves strain and function 16S rRNA sequencing Quotation withheld because this record is not cleared for redistribution. microbiome microbiome Quotation withheld because this record is not cleared for redistribution. disease state disease state Quotation withheld because this record is not cleared for redistribution.

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