Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism

Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism Douglas J. Morrison Tom Preston

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Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism 2016 Gut Microbes 10.1080/19490976.2015.1134082 morrison2016-formation-of-short-chain-fatty-aci morrison2016-formation-of-short-chain-fatty-aci.txt, the project's staged copy b2971bb202ad4e7b449937e17555c8544e68b286 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 short chain fatty acids as signalling molecules between the gut microbiota and human metabolism Quotation withheld because this record is not cleared for redistribution. whether short chain fatty acids are the key molecular link between diet, the microbiome and host health, and what the evidence for that actually supports Quotation withheld because this record is not cleared for redistribution. an integrated review of SCFA across gut, liver and periphery which states, as its own finding, that the field has no method to measure SCFA production in humans and that the animal doses behind its mechanisms are far above habitual human intake Quotation withheld because this record is not cleared for redistribution. mechanism Quotation withheld because this record is not cleared for redistribution. SCFA produced by saccharolytic fermentation in the colon act on gut epithelium, liver and peripheral tissues along a falling concentration gradient Quotation withheld because this record is not cleared for redistribution. review review Quotation withheld because this record is not cleared for redistribution. butyrate raises intestinal barrier integrity by increasing claudin-1 and ZO-1 expression and redistributing occludin - the tight junction proteins Quotation withheld because this record is not cleared for redistribution. in the liver propionate is gluconeogenic while acetate and butyrate are lipogenic, so the propionate:acetate ratio determines how much colonic carbon reaches lipid stores Quotation withheld because this record is not cleared for redistribution. butyrate is the preferred fuel of the colonocyte and the gut epithelium is where it is sequestered - the paper's own reason for the steep epithelial step in the gradient Quotation withheld because this record is not cleared for redistribution. THE PAPER NAMES ITS OWN MECHANISM'S EXCEPTION IN THE NEXT SENTENCE: the `butyrate paradox` - proliferation in healthy colonocytes, apoptosis in transformed ones - is followed immediately by a mouse model where butyrate fuels hyper-proliferation in MSH2-deficient cells and enhances tumour formation Quotation withheld because this record is not cleared for redistribution. THE FIELD HAS NO METHOD TO MEASURE ITS PRIMARY VARIABLE: SCFA production cannot be measured directly in humans, and it is unclear whether stool SCFA output - what is measured instead - is a suitable proxy for luminal production Quotation withheld because this record is not cleared for redistribution. the appetite-regulation mechanism cannot be attributed to SCFA at all until such a method exists, which the authors state as a condition rather than a caveat Quotation withheld because this record is not cleared for redistribution. the human evidence is associative rather than interventional, so high-level evidence from controlled trials is largely lacking Quotation withheld because this record is not cleared for redistribution. there is insufficient evidence to inform any evidence-based clinical or public health intervention using SCFA formulations - stated in the paper's own introduction Quotation withheld because this record is not cleared for redistribution. whether oral SCFA feeding in animals, which produces circulating concentrations far above the human normal range, is an appropriate model for human SCFA physiology requires further validation Quotation withheld because this record is not cleared for redistribution. whether SCFA play an important role in mucosal maintenance and integrity in HUMAN models is stated by the authors as urgently needing further work Quotation withheld because this record is not cleared for redistribution. dry matter intake, a livestock-nutrition unit, used to convert rodent dietary fibre loadings into a comparable human daily intake Quotation withheld because this record is not cleared for redistribution. the animal fibre dose is converted to a human-equivalent intake using national survey data before the animal findings are used eliminates: an effect produced only by a dose no human diet reaches being read as a statement about human physiology · outcome: failed Quotation withheld because this record is not cleared for redistribution. circulating SCFA concentrations in oral-feeding animal models are compared with the human normal range eliminates: a concentration that is pathological in humans being treated as the physiological range · outcome: failed Quotation withheld because this record is not cleared for redistribution. the size of colonic propionate production is set against endogenous glucose production before propionate is called gluconeogenic at the whole-body level eliminates: a real but negligible flux being reported as a contributor to glucose homeostasis · outcome: held Quotation withheld because this record is not cleared for redistribution. SCFA SCFA Quotation withheld because this record is not cleared for redistribution. butyrate butyrate Quotation withheld because this record is not cleared for redistribution. propionate propionate Quotation withheld because this record is not cleared for redistribution. biological gradient biological gradient Quotation withheld because this record is not cleared for redistribution. cross-talk cross-talk Quotation withheld because this record is not cleared for redistribution. molecular signaling molecular signaling Quotation withheld because this record is not cleared for redistribution. acetate acetate Quotation withheld because this record is not cleared for redistribution. intestinal barrier function intestinal barrier function Quotation withheld because this record is not cleared for redistribution. high-fiber diets high-fiber diets Quotation withheld because this record is not cleared for redistribution. energy harvesting energy harvesting Quotation withheld because this record is not cleared for redistribution. SCFA - AS DEFINED HERE: the primary end-products of fermentation of non-digestible carbohydrate that reach the gut microbiota, and the major flow of carbon from the diet through the microbiome to the host Quotation withheld because this record is not cleared for redistribution. SCFA production - the quantity every claim in this literature is about, and the one with no method behind it in humans; STOOL SCFA OUTPUT is what is measured and its adequacy as a proxy is explicitly unsettled Quotation withheld because this record is not cleared for redistribution. the biological gradient - SCFA concentration falling from gut lumen to periphery, so `an SCFA effect` is not one quantity but a different exposure in every tissue Quotation withheld because this record is not cleared for redistribution. claim_type: mechanism a second reading reaching the same value. Recorded: mechanism — note: A BLIND second reading by the project on 2026-08-25: the record's own claim type/method/phenomenon were not looked at until every value here was written and substring-verified. Not applied - a person decides. Sampling frame: the 504 staged records carrying no alternatives block, so this never re-measures the 202. All 11 records with 130+ tags were taken as a census and 19 more spread one per discipline across 22 disciplines - the dense non-neuroscience cell is the one the 202 do not contain (inside them, 94-100% of the densest bands are neuroscience; among these 11, one is)., Quotation withheld because this record is not cleared for redistribution. method: review a second reading DIFFERING from the recorded value. Recorded: review — note: A BLIND second reading by the project on 2026-08-25: the record's own claim type/method/phenomenon were not looked at until every value here was written and substring-verified. Not applied - a person decides. Sampling frame: the 504 staged records carrying no alternatives block, so this never re-measures the 202. All 11 records with 130+ tags were taken as a census and 19 more spread one per discipline across 22 disciplines - the dense non-neuroscience cell is the one the 202 do not contain (inside them, 94-100% of the densest bands are neuroscience; among these 11, one is)., Quotation withheld because this record is not cleared for redistribution. phenomenon: how short chain fatty acids are formed by gut microbial fermentation and how they act on host metabolism a second reading DIFFERING from the recorded value. Recorded: SCFA produced by saccharolytic fermentation in the colon act on gut epithelium, liver and peripheral tissues along a fal — note: A BLIND second reading by the project on 2026-08-25: the record's own claim type/method/phenomenon were not looked at until every value here was written and substring-verified. Not applied - a person decides. Sampling frame: the 504 staged records carrying no alternatives block, so this never re-measures the 202. All 11 records with 130+ tags were taken as a census and 19 more spread one per discipline across 22 disciplines - the dense non-neuroscience cell is the one the 202 do not contain (inside them, 94-100% of the densest bands are neuroscience; among these 11, one is)., Quotation withheld because this record is not cleared for redistribution. critiques → the animal SCFA literature, on the ground that its fibre loadings translate to 20.9-83.7 g/d for men against a habitual UK intake of 14.7 g/d Quotation withheld because this record is not cleared for redistribution. critiques → the human SCFA literature, on the ground that it rests on association rather than intervention and on stool output rather than production Quotation withheld because this record is not cleared for redistribution. extends → the seminal sudden-death-victim measurements of SCFA across the gut epithelium and liver, which this review turns into a general principle about tissue exposure Quotation withheld because this record is not cleared for redistribution. cross-talk —same-as→ molecular signaling cross-talk molecular signaling the relation itself is separately evidenced · strength of the relation: 0.9 · the relation stated: the review names the intricate molecular signalling between gut microbiome and host 'cross-talk', in quotation marks, and uses the metaphor thereafter Quotation withheld because this record is not cleared for redistribution. propionate —distinct-from→ acetate propionate acetate differs in: metabolic fate in the liver: gluconeogenesis against lipogenesis · the relation itself is separately evidenced · strength of the relation: 0.95 · differs in (stated by the tagger, no quotation): metabolic fate in the liver: gluconeogenesis against lipogenesis · the relation stated: in the liver they have OPPOSITE fates - propionate gluconeogenic, acetate lipogenic - so the two cannot be pooled as 'SCFA' for any metabolic claim Quotation withheld because this record is not cleared for redistribution. energy harvesting —contrasted-with→ high-fiber diets energy harvesting high-fiber diets differs in: direction of the predicted effect of fermentation on body weight · the relation itself is separately evidenced · strength of the relation: 0.9 · differs in (stated by the tagger, no quotation): direction of the predicted effect of fermentation on body weight · the relation stated: the energy-harvesting hypothesis predicts SCFA add calories in the obese; the observational human evidence runs the other way and the paper says so Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span says the energy-harvesting hypothesis is not supported by evidence that high-fiber diets protect against weight gain; contrasted-with is loose. Quotation withheld because this record is not cleared for redistribution. butyrate —causes→ intestinal barrier function butyrate intestinal barrier function the relation itself is separately evidenced · strength of the relation: 0.9 · the relation stated: butyrate enhances barrier function through increased claudin-1 and ZO-1 expression and occludin redistribution Quotation withheld because this record is not cleared for redistribution. SCFA production cannot be measured directly in humans and stool SCFA output, the measurement used instead, is of unestablished adequacy as a proxy for luminal production SCFA production cannot be measured directly in humans and stool SCFA output, the measurement used instead, is of unestablished adequacy as a proxy for luminal production Quotation withheld because this record is not cleared for redistribution. the animal fibre doses behind the SCFA mechanisms translate to 20.9-83.7 g/d for men, against a measured habitual UK intake of 14.7 g/d - even the lowest animal dose is a substantial increase over what people eat the animal fibre doses behind the SCFA mechanisms translate to 20.9-83.7 g/d for men, against a measured habitual UK intake of 14.7 g/d - even the lowest animal dose is a substantial increase over what people eat Quotation withheld because this record is not cleared for redistribution. A strong gradient for each SCFA from gut lumen to periphery gives differing cell and tissue exposure. A strong gradient for each SCFA from gut lumen to periphery gives differing cell and tissue exposure. Quotation withheld because this record is not cleared for redistribution. a small number of organisms - F. prausnitzii, E. rectale, E. hallii, R. bromii - are responsible for the major fraction of butyrate production a small number of organisms - F. prausnitzii, E. rectale, E. hallii, R. bromii - are responsible for the major fraction of butyrate production Quotation withheld because this record is not cleared for redistribution. the energy-harvesting explanation for obesity is not supported by human observational evidence, where high-fibre diets protect against weight gain the energy-harvesting explanation for obesity is not supported by human observational evidence, where high-fibre diets protect against weight gain Quotation withheld because this record is not cleared for redistribution. Microbiota manipulation is highly likely to affect disease risk, but probiotic studies have been far from convincing on metabolic health and weight management. Microbiota manipulation is highly likely to affect disease risk, but probiotic studies have been far from convincing on metabolic health and weight management. Quotation withheld because this record is not cleared for redistribution. the primary end-products of fermentation of non-digestible carbohydrates available to the gut microbiota, and the major flow of carbon from diet through microbiome to host short chain fatty acids (SCFA) Quotation withheld because this record is not cleared for redistribution. butyrate induces proliferation in healthy colonocytes but terminal differentiation and apoptosis in transformed cells - a dual role the field has named butyrate paradox Quotation withheld because this record is not cleared for redistribution. the proposal that SCFA contribute additional calories through fermentation in the obese, offered as an explanation for additional weight gain “energy harvesting” hypothesis Quotation withheld because this record is not cleared for redistribution. g/d, mean dietary fibre intake for UK men aged 19-64, against a 20.9-83.7 g/d animal-equivalent supplementation range 14.7 Quotation withheld because this record is not cleared for redistribution. mg/kg/day of propionate for an 85 kg human, against endogenous glucose production of 2.2 mg/kg/min of which about 50% is gluconeogenic 29.5 Quotation withheld because this record is not cleared for redistribution. per cent - the estimated gut-microbiota-derived share of whole-body acetate flux, with the effect of different NDCs on that share largely unknown 44 Quotation withheld because this record is not cleared for redistribution. per cent reduction in serum free fatty acids after rectal infusion of acetate and propionate 40 Quotation withheld because this record is not cleared for redistribution. g/d of supplemented fibre, about 5-10% of dry matter intake, needed to induce appetite-regulation effects in the human studies that found them 16 - 35 Quotation withheld because this record is not cleared for redistribution. normal range normal range Quotation withheld because this record is not cleared for redistribution. dietary fiber supplementation dietary fiber supplementation Quotation withheld because this record is not cleared for redistribution. tissue tissue Quotation withheld because this record is not cleared for redistribution. stool SCFA output stool SCFA output Quotation withheld because this record is not cleared for redistribution.

The full text of this article is not redistributable, so it is not included here. The evidence sentences are withheld with it; the tag layer and its grounding status remain. The article itself is at https://doi.org/10.1080/19490976.2015.1134082.