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Cited by 2,375Gut microbiota and healthProbiotics and Fermented FoodsInfant Nutrition and Health

Role of the gut microbiota in nutrition and health

Open access
Valdes, Ana M, Walter, Jens, Segal, Eran, Spector, Tim D·2018·BMJ
DOI 10.1136/bmj.k2179PMC PMC6000740
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Abstract

Ana M Valdes and colleagues discuss strategies for modulating the gut microbiota through diet and probiotics

AI snapshot

Written from the paper’s full text.

TL;DR

This review summarizes evidence that the gut microbiota influences nutrition and health, with diet, drugs, and probiotics as key modulators. It highlights fibre/prebiotics and probiotics as promising interventions while noting evidence gaps and heterogeneity.

Key findings

  • The gut microbiota is described as a virtual organ: approximately 100 trillion micro-organisms inhabit the human gastrointestinal tract, and the microbiome encodes over three million genes compared with about 23,000 in the human genome, producing thousands of metabolites that influence host fitness, phenotype, and health.
  • Lower bacterial diversity is reproducibly observed in inflammatory bowel disease, psoriatic arthritis, type 1 diabetes, atopic eczema, coeliac disease, obesity, type 2 diabetes, and arterial stiffness; long-term weight gain over 10 years correlates with low microbiota diversity, exacerbated by low dietary fibre intake.
  • Diet and medication strongly influence microbiota composition; a large Dutch-Belgian population study found drugs explained 10% of community variation, and fibre/prebiotics increased microbiota diversity and SCFA production, with links to reduced type 2 diabetes and cardiovascular disease.
  • A review of 22 systematic reviews covering 313 trials and 46,826 participants found probiotic benefits for preventing *Clostridium difficile* diarrhoea (RR 0.30, 95% CI 0.21 to 0.42), necrotising enterocolitis (RR 0.43, 95% CI 0.33 to 0.56), antibiotic-associated diarrhoea in children (RR 0.46, 95% CI 0.35 to 0.61), and eczema in infants/children (RR 0.74, 95% CI 0.67 to 0.82).

Methods

  • Narrative review article synthesizing evidence on gut microbiota, nutrition, and health, including definitions, tables of dietary effects, and a summary of probiotic systematic reviews.
  • For probiotics, the authors searched the Cochrane library for “probiotic*” (39 studies) and Medline for “systematic review” or “meta-analysis” and “probiotic*” (31 studies), including 22 systematic reviews of randomised controlled trials published in the past five years, totaling 313 trials and 46,826 participants.
  • Main analysis is narrative synthesis of animal, observational, and interventional human studies; no formal meta-analysis is reported for the review as a whole.

Limitations

  • The paper states that animal model findings have unknown translation to humans, observational studies cannot measure causal relations, and probiotic studies were heterogeneous and not necessarily matched for type or dose of probiotic or length of intervention, limiting precise recommendations.
  • The paper states insufficient clinical evidence exists to draw clear conclusions or recommendations for restrictive diets and other dietary preferences based on gut microbiota, and calls for randomised controlled studies using consistent matrices.
  • Evident from the text: as a narrative review, selection and synthesis methods for non-probiotic sections are not systematically described, and many conclusions rely on animal models or cross-sectional associations.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1136/bmj.k2179

Cites

143 of 143 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 133 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Randomised controlled trials have shown that higher production of short chain fatty acids correlates with lower diet-induced obesity.

    “Randomised controlled trials have shown that higher production of SCFAs correlates with lower diet-induced obesity21 and with reduced insulin resistance.22”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Lin HV Frassetto A Kowalik EJ Jr Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One 2012; 7: e35240. 10.1371/journal.pone.0035240 22506074 PMC3323649

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  • Premisecitation

    Randomised controlled trials have shown that higher production of short chain fatty acids correlates with reduced insulin resistance.

    “Randomised controlled trials have shown that higher production of SCFAs correlates with lower diet-induced obesity21 and with reduced insulin resistance.22”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Zhao L Zhang F Ding X Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 2018; 359: 1151- 6. 10.1126/science.aao5774 29590046

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  • Premisecitation

    This fermentation supports the growth of specialist microbes that produce short chain fatty acids and gases.

    “This fermentation supports the growth of specialist microbes that produce short chain fatty acids (SCFAs) and gases.17”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Wong JM de Souza R Kendall CW Emam A Jenkins DJ Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol 2006; 40: 235- 43. 10.1097/00004836-200603000-00015 16633129

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  • Premisecitation

    The gut microbiota provides essential capacities for the fermentation of non-digestible substrates like dietary fibres and endogenous intestinal mucus.

    “The gut microbiota provides essential capacities for the fermentation of non-digestible substrates like dietary fibres and endogenous intestinal mucus.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Wong JM de Souza R Kendall CW Emam A Jenkins DJ Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol 2006; 40: 235- 43. 10.1097/00004836-200603000-00015 16633129

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  • Premisecitation

    The major short chain fatty acids produced are acetate, propionate, and butyrate.

    “The major SCFAs produced are acetate, propionate, and butyrate.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Wong JM de Souza R Kendall CW Emam A Jenkins DJ Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol 2006; 40: 235- 43. 10.1097/00004836-200603000-00015 16633129

      Not checked in the free run.

  • May combine two claims. 47
  • Classified as probably not a substantial claim. 9

  • May combine two claims.

    Findingown data

    Probiotics also seem to improve cardiometabolic parameters and reduced serum concentration of C reactive protein in patients with type 2 diabetes.

    “Probiotics also seem to improve cardiometabolic parameters and reduced serum concentrationof C reactive protein in patients with type 2 diabetes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The analysis of 313 trials and 46,826 participants showed substantial evidence for beneficial effects of probiotic supplementation in preventing diarrhoea, necrotising enterocolitis, acute upper respiratory tract infections, pulmonary exacerbations in children with cystic fibrosis, and eczema in children.

    “The analysis of 313 trials and 46 826 participants showed substantial evidence for beneficial effects of probiotic supplementation in preventing diarrhoea, necrotising enterocolitis, acute upper respiratory tract infections, pulmonary exacerbations in children with cystic fibrosis, and eczema in children.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    In humans, observational studies can show cross-sectional associations between microbes and health traits but are limited by the inability to measure causal relations.

    “In humans, observational studies can show cross-sectional associations between microbes and health traits but are limited by the inability to measure causal relations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Butyrate is essential for epithelial cells to consume large amounts of oxygen through beta oxidation, generating a state of hypoxia that maintains oxygen balance in the gut, preventing gut microbiota dysbiosis.

    “Butyrate is essential for epithelial cells to consume large amounts of oxygen through β oxidation, generating a state of hypoxia that maintains oxygen balance in the gut, preventing gut microbiota dysbiosis.19”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Byndloss MX Olsan EE Rivera-Chávez F Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. Science 2017; 357: 570- 5. 10.1126/science.aam9949 28798125 PMC5642957

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationnone given

    Animal models can help identify gut microbes and mechanisms, though the degree to which findings translate to humans is unknown.

    “Animal models can help identify gut microbes and mechanisms, though the degree to which findings translate to humans is unknown.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Acetate reaches peripheral tissues where it is used in cholesterol metabolism and lipogenesis, and may play a role in central appetite regulation.

    “Acetate—the most abundant SCFA and an essential metabolite for the growth of other bacteria—reaches the peripheral tissues where it is used in cholesterol metabolism and lipogenesis, and may play a role in central appetite regulation.20”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Frost G Sleeth ML Sahuri-Arisoylu M The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun 2014; 5: 3611. 10.1038/ncomms4611 24781306 PMC4015327

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    Premisecitation

    Butyrate can activate intestinal gluconeogenesis, having beneficial effects on glucose and energy homeostasis.

    “Butyrate is the main energy source for human colonocytes, can induce apoptosis of colon cancer cells, and can activate intestinal gluconeogenesis, having beneficial effects on glucose and energy homeostasis.18”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] De Vadder F Kovatcheva-Datchary P Goncalves D Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 2014; 156: 84- 96. 10.1016/j.cell.2013.12.016 24412651

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    Premisecitation

    Butyrate and propionate, but not acetate, seem to control gut hormones and reduce appetite and food intake in mice.

    “Butyrate and propionate, but not acetate, seem to control gut hormones and reduce appetite and food intake in mice.21”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Lin HV Frassetto A Kowalik EJ Jr Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One 2012; 7: e35240. 10.1371/journal.pone.0035240 22506074 PMC3323649

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Acetate is the most abundant short chain fatty acid and an essential metabolite for the growth of other bacteria.

    “Acetate—the most abundant SCFA and an essential metabolite for the growth of other bacteria—reaches the peripheral tissues where it is used in cholesterol metabolism and lipogenesis, and may play a role in central appetite regulation.20”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Frost G Sleeth ML Sahuri-Arisoylu M The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun 2014; 5: 3611. 10.1038/ncomms4611 24781306 PMC4015327

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Twin studies show that gut microbiota has a heritable component, but environmental factors related to diet, drugs, and anthropometric measures are larger determinants of microbiota composition.

    “Twin studies have shown that, although there is a heritable component to gut microbiota, environmental factors related to diet, drugs, and anthropometric measures are larger determinants of microbiota composition.4 5”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4] Goodrich JK Waters JL Poole AC Human genetics shape the gut microbiome. Cell 2014; 159: 789- 99. 10.1016/j.cell.2014.09.053 25417156 PMC4255478

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    • cites [5] Rothschild D Weissbrod O Barkan E Environment dominates over host genetics in shaping human gut microbiota. Nature 2018; 555: 210- 5. 10.1038/nature25973 29489753

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    Premisecitation

    Recent interventional studies indicate that major increases in dietary fibre can temporarily reduce diversity, as the microbes that digest fibre become specifically enriched, leading to a change in composition and, through competitive interactions, reduced diversity.

    “But recent interventional studies indicate that major increases in dietary fibre can temporarily reduce diversity, as the microbes that digest fibre become specifically enriched, leading to a change in composition and, through competitive interactions, reduced diversity.22”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Zhao L Zhang F Ding X Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 2018; 359: 1151- 6. 10.1126/science.aao5774 29590046

      Not checked in the free run.

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    Premisenone given

    Specific foods and dietary patterns can influence the abundance of different types of bacteria in the gut, which in turn can affect health.

    “Specific foods and dietary patterns can all influence the abundance of different types of bacteria in the gut, which in turn can affect health (table 1).”
    Quote in the paperNot a substantial claim

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    Premisecitation

    A large study of UK twins found that the genus Christensenella was rare in overweight people and when given to germ free mice prevented weight gain.

    “A large study of UK twins found that the genus Christensenella was rare in overweight people and when given to germ free mice prevented weight gain.4”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Goodrich JK Waters JL Poole AC Human genetics shape the gut microbiome. Cell 2014; 159: 789- 99. 10.1016/j.cell.2014.09.053 25417156 PMC4255478

      Not checked in the free run.

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    Premisecitation

    Trimethylamine is oxidised in the liver to trimethylamine N-oxide, which is positively associated with an increased risk of atherosclerosis and major adverse cardiovascular events.

    “Trimethylamine is oxidised in the liver to trimethylamine N-oxide, which is positively associated with an increased risk of atherosclerosis and major adverse cardiovascular events.24”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Tang WH Wang Z Levison BS Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 2013; 368: 1575- 84. 10.1056/NEJMoa1109400 23614584 PMC3701945

      Not checked in the free run.

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    Premisecitation

    Long term weight gain over 10 years in humans correlates with low microbiota diversity, and this association is exacerbated by low dietary fibre intake.

    “Although much of the confirmatory evidence comes from mouse models, long term weight gain (over 10 years) in humans correlates with low microbiota diversity, and this association is exacerbated by low dietary fibre intake.28”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Menni C Jackson MA Pallister T Steves CJ Spector TD Valdes AM Gut microbiome diversity and high-fibre intake are related to lower long-term weight gain. Int J Obes (Lond) 2017; 41: 1099- 105. 10.1038/ijo.2017.66 28286339 PMC5500185

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    Premisecitation

    The production of trimethylamine from dietary phosphatidylcholine and carnitine depends on the gut microbiota, and thus its amount in blood varies between people.

    “The production of trimethylamine from dietary phosphatidylcholine and carnitine (from meat and dairy) depends on the gut microbiota and thus its amount in blood varies between people.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Tang WH Wang Z Levison BS Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 2013; 368: 1575- 84. 10.1056/NEJMoa1109400 23614584 PMC3701945

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    Premisecitation

    Faecal microbiota transplantation is effective in cases of severe drug refractory Clostridium difficile infection and is now routinely used for this purpose around the world.

    “This procedure is effective in cases of severe drug refractory Clostridium difficile infection and is now routinely used for this purpose around the world.43”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Schneider KM Wirtz TH Kroy D Successful fecal microbiota transplantation in a patient with severe complicated Clostridium difficile infection after liver transplantation. Case Rep Gastroenterol 2018; 12: 76- 84. 10.1159/000481937 29606940 PMC5869577

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    Premisecitation

    Mice given sucralose for six months had an increase in the expression in the gut of bacterial pro-inflammatory genes and disrupted faecal metabolites.

    “Mice given sucralose for six months had an increase in the expression in the gut of bacterial pro-inflammatory genes and disrupted faecal metabolites.48”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48] Bian X Chi L Gao B Tu P Ru H Lu K Gut microbiome response to sucralose and its potential role in inducing liver inflammation in mice. Front Physiol 2017; 8: 487. 10.3389/fphys.2017.00487 28790923 PMC5522834

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  • May combine two claims.

    Interpretationreasoning

    The association between reduced diversity and disease indicates that a species-rich gut ecosystem is more robust against environmental influences, as functionally related microbes in an intact ecosystem can compensate for the function of other missing species.

    “The association between reduced diversity and disease indicates that a species-rich gut ecosystem is more robust against environmental influences, as functionally related microbes in an intact ecosystem can compensate for the function of other missing species.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    For other pathologies, faecal transplants are not yet clinical practice but have been explored.

    “For other pathologies, faecal transplants are not yet clinical practice but have been explored.44”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Cammarota G Ianiro G Tilg H European FMT Working Group European consensus conference on faecal microbiota transplantation in clinical practice. Gut 2017; 66: 569- 80. 10.1136/gutjnl-2016-313017 28087657 PMC5529972

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    Premisecitation

    In mice fed emulsifiers, Bacteroidales and Verrucomicrobia were decreased and inflammation promoting Proteobacteria associated with mucus was enriched.

    “Bacteroidales and Verrucomicrobia were decreased and inflammation promoting Proteobacteria associated with mucus was enriched .49”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [49] Chassaing B Koren O Goodrich JK Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature 2015; 519: 92- 6. 10.1038/nature14232 25731162 PMC4910713

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    Premisecitation

    Healthy microbiota are resilient to temporal changes by dietary interventions, meaning that homeostatic reactions restore the original community composition, as recently shown in the case of bread.

    “But healthy microbiota are resilient to temporal changes by dietary interventions, meaning that homeostatic reactions restore the original community composition, as recently shown in the case of bread 68”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Korem T, Zeevi D, Zmora N, et al. Bread affects clinical parameters and induces gut microbiome-associated personal glycemic responses. Cell Metabolism. 2017; 25: 1243-53 e5. 28591632

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    Premisecitation

    Pesticides and other chemicals are commonly sprayed on foods, but solid evidence for their harm on gut health and the effects of organic food is currently lacking.

    “Pesticides and other chemicals are commonly sprayed on foods, but, although levels can be high, solid evidence for their harm on gut health and the effects of organic food is currently lacking.63”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] Lee YM Kim KS Jacobs DR Jr Lee DH Persistent organic pollutants in adipose tissue should be considered in obesity research. Obes Rev 2017; 18: 129- 39. 10.1111/obr.12481 27911986

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    Premisecitation

    Humans have very variable responses to antibiotics, and intervention studies have not shown consistent metabolic consequences.

    “But humans have very variable responses to antibiotics, and intervention studies have not shown consistent metabolic consequences.62”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [62] Reijnders D Goossens GH Hermes GD Effects of gut microbiota manipulation by antibiotics on host metabolism in obese humans: A randomized double-blind placebo-controlled trial. Cell Metab 2016; 24: 63- 74. 10.1016/j.cmet.2016.06.016 27411009

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    Premisecitation

    The low FODMAP diet is associated with a reduced proportion of Bifidobacterium in patients with irritable bowel syndrome, and responsiveness to this diet can be predicted by faecal bacterial profiles.

    “It is associated with a reduced proportion of Bifidobacterium in patients with irritable bowel syndrome, and responsiveness to this diet can be predicted by faecal bacterial profiles.57”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Bennet SMP Bohn L Storsrud S Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs. Gut 2017. 28416515

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  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Probiotic supplementation has several beneficial effects on human health.

    “Probiotic supplementation has several beneficial effects on human health”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Increased abundance of known butyrate producing bacteria in the African Americans consuming a rural African diet caused butyrate production to increase 2.5 times and reduced synthesis of secondary bile acid.

    “Increased abundance of known butyrate producing bacteria in the African Americans consuming a rural African diet caused butyrate production to increase 2.5 times and reduced synthesis of secondary bile acid.66”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [66] O'Keefe SJ, Li JV and Lahti L. Fat, fibre and cancer risk in African Americans and rural Africans. 2015; 6: 6342. PMC4415091 25919227

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    Premisecitation

    A controlled feeding experiment of 10 human omnivores randomised to receive either a high fat and low fibre diet or a low fat and high fibre diet for 10 days found very modest effects on gut microbiome composition and no difference in short chain fatty acid production.

    “A controlled feeding experiment of 10 human omnivores randomised to receive either a high fat and low fibre diet or a low fat and high fibre for 10 days found very modest effects on gut microbiome composition and no difference in short chain fatty acid production.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] Wu GD Compher C Chen EZ Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production. Gut 2016; 65: 63- 72. 10.1136/gutjnl-2014-308209 25431456 PMC4583329

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    Premisecitation

    Other studies have shown major effects of commonly prescribed proton pump inhibitors on the microbial community, which could explain higher rates of gastrointestinal infection in people taking these drugs.

    “Other studies have shown major effects of commonly prescribed proton pump inhibitors on the microbial community, which could explain higher rates of gastrointestinal infection in people taking these drugs.60”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Jackson MA Goodrich JK Maxan ME Proton pump inhibitors alter the composition of the gut microbiota. Gut 2016; 65: 749- 56. 10.1136/gutjnl-2015-310861 26719299 PMC4853574

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    Premisecitation

    Microbiome composition defines glucose response to foods and can be used to personalise diet.

    “Microbiome composition defines glucose response to foods and can be used to personalise diet94”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [94] Zeevi D Korem T Zmora N Personalized nutrition by prediction of glycemic responses. Cell 2015; 163: 1079- 94. 10.1016/j.cell.2015.11.001 26590418

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  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Dietary amounts of protein, saturated and unsaturated fats, carbohydrates, and dietary fibre influence the abundance of different types of bacteria in the gut.

    “Dietary amounts of protein, saturated and unsaturated fats, carbohydrates, and dietary fibre influence the abundance of different types of bacteria in the gut.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    The taxa enriched differ depending on the type of resistant starches and other dietary fibres, indicating that shifts are dependent on the carbohydrate's chemical structure and the microbes' enzymatic capacity to access them.

    “The taxa enriched differ depending on the type of resistant starches and other dietary fibres,75 indicating that shifts are dependent on the carbohydrate’s chemical structure and the microbes’ enzymatic capacity to access them.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [75] Martínez I Kim J Duffy PR Schlegel VL Walter J Resistant starches types 2 and 4 have differential effects on the composition of the fecal microbiota in human subjects. PLoS One 2010; 5: e15046. 10.1371/journal.pone.0015046 21151493 PMC2993935

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  • May combine two claims.

    Premisecitation

    Low FODMAP diets lead to profound changes in the microbiota and metabolome, the duration and clinical relevance of which are as yet unknown.

    “Low FODMAP diets lead to profound changes in the microbiota and metabolome, the duration and clinical relevance of which are as yet unknown.58 59”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [58] McIntosh K Reed DE Schneider T FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial. Gut 2017; 66: 1241- 51. 10.1136/gutjnl-2015-311339 26976734

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    • cites [59] Staudacher HM Whelan K The low FODMAP diet: recent advances in understanding its mechanisms and efficacy in IBS. Gut 2017; 66: 1517- 27. 10.1136/gutjnl-2017-313750 28592442

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  • May combine two claims.

    Premisecitation

    Microbes need to adhere to a substrate and tolerate the conditions generated from fermentation (such as low pH).

    “Microbes need also to “adhere” to a substrate and tolerate the conditions generated from fermentation (such as low pH).76”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [76] Koropatkin NM Cameron EA Martens EC How glycan metabolism shapes the human gut microbiota. Nat Rev Microbiol 2012; 10: 323- 35. 10.1038/nrmicro2746 22491358 PMC4005082

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  • May combine two claims.

    Premisecitation

    Dietary fibre intake influences gut microbiota composition and is related to better health.

    “Dietary fibre intake influences gut microbiota composition and is related to better health86 87 104”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [86] Veronese N Solmi M Caruso MG Dietary fiber and health outcomes: an umbrella review of systematic reviews and meta-analyses. Am J Clin Nutr 2018; 107: 436- 44. 10.1093/ajcn/nqx082 29566200

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    • cites [87] Thompson SV Hannon BA An R Holscher HD Effects of isolated soluble fiber supplementation on body weight, glycemia, and insulinemia in adults with overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr 2017; 106: 1514- 28. 10.3945/ajcn.117.163246 29092878

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    • cites [104]

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  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    The microbiota can also be modified by adding live micro-organisms to food or by periods of fasting.

    “The microbiota can also be modified by adding live micro-organisms to food or by periods of fasting.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    One study showed that 21 healthy people had substantially different gut microbiota profiles after four weeks on a gluten-free diet, and most people showed a lower abundance of several key beneficial microbe species.

    “One study showed that 21 healthy people had substantially different gut microbiota profiles after four weeks on a gluten-free diet. Most people showed a lower abundance of several key beneficial microbe species.54”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Bonder MJ Tigchelaar EF Cai X The influence of a short-term gluten-free diet on the human gut microbiome. Genome Med 2016; 8: 45. 10.1186/s13073-016-0295-y 27102333 PMC4841035

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  • May combine two claims.

    Premisecitation

    A recent large observational study showed an increased risk of heart disease in gluten avoiders, potentially because of the reduced consumption of whole grains.

    “But most people who avoid gluten do not have coeliac disease or proved intolerance, and a recent large observational study showed an increased risk of heart disease in gluten avoiders, potentially because of the reduced consumption of whole grains.53”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [53] Lebwohl B Cao Y Zong G Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study. BMJ 2017; 357: j1892. 10.1136/bmj.j1892 28465308 PMC5421459

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    • Rests on an assumption: Most people who avoid gluten do not have coeliac disease or proved intolerance.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Diet and medication have a strong influence on gut microbiota composition.

    “Diet and medication have a strong influence on gut microbiota composition”
    Quote in the paperNot a substantial claim

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    Premisenone given

    Antibiotics clearly have an effect on gut microbes, and low doses are routinely given to livestock to increase their growth and weight.

    “Antibiotics clearly have an effect on gut microbes, and low doses are routinely given to livestock to increase their growth and weight.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    These changes only last as long as the carbohydrate is consumed, and they are highly individual, which provides a basis for personalised approaches.

    “These changes only last as long as the carbohydrate is consumed, and they are highly individual, which provides a basis for personalised approaches.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [75] Martínez I Kim J Duffy PR Schlegel VL Walter J Resistant starches types 2 and 4 have differential effects on the composition of the fecal microbiota in human subjects. PLoS One 2010; 5: e15046. 10.1371/journal.pone.0015046 21151493 PMC2993935

      Not checked in the free run.

    • cites [77] Walker AW Ince J Duncan SH Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J 2011; 5: 220- 30. 10.1038/ismej.2010.118 20686513 PMC3105703

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Changes to the gut microbiota can occur within days of changing diet; remarkable differences were found after African Americans and rural Africans switched diets for only two weeks.

    “Changes to the gut microbiota can occur within days of changing diet; remarkable differences were found after African Americans and rural Africans switched diets for only two weeks.66”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [66] O'Keefe SJ, Li JV and Lahti L. Fat, fibre and cancer risk in African Americans and rural Africans. 2015; 6: 6342. PMC4415091 25919227

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A study of 15 vegans and 16 omnivores found striking differences in serum metabolites generated by the gut microbes but very modest differences in gut bacterial communities.

    “A study of 15 vegans and 16 ominvores found striking differences in serum metabolites generated by the gut microbes but very modest differences in gut bacterial communities.50”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] Wu GD Compher C Chen EZ Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production. Gut 2016; 65: 63- 72. 10.1136/gutjnl-2014-308209 25431456 PMC4583329

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Many short term feeding trials with purified dietary fibres or even whole plant based diets either have no effect on microbiota diversity or reduce it, but can still have clinical benefits, potentially through metabolites such as small chain fatty acids.

    “Many short term feeding trials with purified dietary fibres or even whole plant based diets either have no effect on microbiota diversity or reduce it,22 but can still have clinical benefits, potentially through metabolites such as small chain fatty acids.22 67”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [22] Zhao L Zhang F Ding X Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 2018; 359: 1151- 6. 10.1126/science.aao5774 29590046

      Not checked in the free run.

    • cites [67] David LA Maurice CF Carmody RN Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014; 505: 559- 63. 10.1038/nature12820 24336217 PMC3957428

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Stable engraftment of a probiotic Bifidobacterium longum has been shown to depend on individualised features of the gut microbiota, providing a rationale for the personalisation of probiotic applications.

    “Stable engraftment of a probiotic Bifidobacterium longum, for example, has been shown to depend on individualised features of the gut microbiota, providing a rationale for the personalisation of probiotic applications.93”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [93] Maldonado-Gómez MX Martínez I Bottacini F Stable engraftment of Bifidobacterium longum AH1206 in the human gut depends on individualized features of the resident microbiome. Cell Host Microbe 2016; 20: 515- 26. 10.1016/j.chom.2016.09.001 27693307

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A recent intervention study found dietary fibres significantly reduced insulin resistance in patients with type 2 diabetes, with clear links to the shifts in the microbiota and beneficial metabolites (such as butyrate).

    “and a recent intervention study found dietary fibres significantly reduced insulin resistance in patients with type 2 diabetes, with clear links to the shifts in the microbiota and beneficial metabolites (such as butyrate).45”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [45] Kootte RS, Levin E, Salojarvi J, et al. Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell metabolism. 2017; 26: 611-9 e6. 28978426

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Fibre consumption is associated with beneficial effects in several contexts.

    “- Fibre consumption is associated with beneficial effects in several contexts”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Gut microbiota influences many areas of human health from innate immunity to appetite and energy metabolism.

    “- Gut microbiota influences many areas of human health from innate immunity to appetite and energy metabolism”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The studies were not homogeneous and were not necessarily matched for type or dose of probiotic supplementation nor length of intervention, which limits precise recommendations.

    “Importantly, the studies were not homogeneous and were not necessarily matched for type or dose of probiotic supplementation nor length of intervention, which limits precise recommendations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Low fibre intake reduces production of small chain fatty acids and shifts the gastrointestinal microbiota metabolism to use less favourable nutrients, leading to the production of potentially detrimental metabolites.

    “Low fibre intake reduces production of small chain fatty acids and shifts the gastrointestinal microbiota metabolism to use less favourable nutrients,78 leading to the production of potentially detrimental metabolites.79 80”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [78] Cummings JH Macfarlane GT The control and consequences of bacterial fermentation in the human colon. J Appl Bacteriol 1991; 70: 443- 59. 10.1111/j.1365-2672.1991.tb02739.x 1938669

      Not checked in the free run.

    • cites [79] Russell WR Gratz SW Duncan SH High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. Am J Clin Nutr 2011; 93: 1062- 72. 10.3945/ajcn.110.002188 21389180

      Not checked in the free run.

    • cites [80] Duncan SH Belenguer A Holtrop G Johnstone AM Flint HJ Lobley GE Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol 2007; 73: 1073- 8. 10.1128/AEM.02340-06 17189447 PMC1828662

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Convincing evidence shows that the low fibre Western diet degrades the colonic mucus barrier, causing microbiota encroachment, which results in pathogen susceptibility and inflammation, providing a potential mechanism for the links of Western diet with chronic diseases.

    “Convincing evidence shows that the low fibre Western diet degrades the colonic mucus barrier, causing microbiota encroachment, which results in pathogen susceptibility81and inflammation,82 providing a potential mechanism for the links of Western diet with chronic diseases.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [81] Desai MS Seekatz AM Koropatkin NM A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 2016; 167: 1339- 1353.e21. 10.1016/j.cell.2016.10.043 27863247 PMC5131798

      Not checked in the free run.

    • cites [82] Earle KA Billings G Sigal M Quantitative imaging of gut microbiota spatial organization. Cell Host Microbe 2015; 18: 478- 88. 10.1016/j.chom.2015.09.002 26439864 PMC4628835

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Drugs, food ingredients, antibiotics, and pesticides could all have adverse effects on the gut microbiota.

    “- Drugs, food ingredients, antibiotics, and pesticides could all have adverse effects on the gut microbiota”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Probiotics can affect health independently of the gut microbiota through direct effects on the host; for example, through immune modulation or the production of bioactive compounds.

    “But probiotics can affect health independently of the gut microbiota through direct effects on the host; for example, through immune modulation or the production of bioactive compounds.”
    Quote in the paperNot a substantial claim
53 of 53

  • The paper relies on this without support.

    Most people who avoid gluten do not have coeliac disease or proved intolerance.

    “But most people who avoid gluten do not have coeliac disease or proved intolerance”

  • The paper relies on this without support.

    The microbiome is best thought of as a virtual organ of the body.

    “the microbiome is now best thought of as a virtual organ of the body.”

  • The paper relies on this without support.

    The strongest level of evidence is obtained from interventional clinical studies, in particular randomised controlled trials.

    “The strongest level of evidence is obtained from interventional clinical studies—in particular, randomised controlled trials.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The gastrointestinal microbiome plays a central role in human health and disease.

    “The gastrointestinal microbiome is now appreciated to play a central role in human health and disease [114,115].”

    From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [115]

  • The core bacterial taxa are resilient to most temporary outside influences, but the gut microbial community as a whole displays a high inter-individual day-to-day variability.

    “While the core bacterial taxa are resilient to most temporary outside influences, the gut microbial community as a whole displays a high inter-individual day-to-day variability [2].”

    From Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration (2019) · cites this paper as [2]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Opposite effects of sucralose on bacterial abundance

    Major

    Table 1 says Bacteroides, Clostridia, and total aerobic bacteria were significantly lower, while the text says rats given sucralose had significantly higher proportions of all three.

  • Diastolic-pressure decrease called significant despite interval crossing zero

    Minor

    The table includes diastolic blood pressure among outcomes said to have significantly decreased, but its stated 95% confidence interval extends from −4.5 to 0.24.

  • LDL estimate falls outside its confidence interval

    Minor

    The reported LDL cholesterol estimate is positive 8.32 mg/dL, whereas both bounds of its stated 95% confidence interval are negative.

  • Citation 45 describes a different intervention and patient group

    Minor

    The text attributes a dietary-fibre intervention in patients with type 2 diabetes to reference 45, whose title instead describes lean-donor faeces in people with metabolic syndrome.

  • Fasting-glucose significance conflicts with its confidence interval

    Minor

    The table reports a significant reduction and P = 0.000, but its 95% confidence interval for the difference includes zero.

5 of 5

Cites

Flagged first, then by citations

2 of the 145 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [103]Administration FaD Code of Federal Regulations Title 21 Subpart E: Specific Requirements for Health Claims [23 pp.] EFSA J 2016; 14: 4369.

Cited by

Sorted by citations

Related

Authors
Valdes, A. M., Walter, J., Segal, E., & Spector, T. D.
Affiliations
  • University of Nottingham (GB)
  • University of Alberta (CA)
  • Weizmann Institute of Science (IL)
  • King's College London (GB)
Corresponding author
Spector, Tim D
ORCID
Venue
BMJ
Publisher
BMJ
Published
2018-06-13
Volume
361
Pages
k2179
ISSN
  • 1756-1833 (ISSN-L)
  • 0959-8138
DOI
10.1136/bmj.k2179
PMC
PMC6000740
OpenAlex
W2808457437
Cited by
2,375
References
145
Citations by year
2026: 234 · 2025: 350 · 2024: 377 · 2023: 418 · 2022: 369 · 2021: 277 · 2020: 213 · 2019: 115 · 2018: 18
FWCI
15.35
Type
journal article
Language
en
Open access
Licence
Locations
  • BMJ (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Wellcome Trust (FP7/2007–2013)
  • Joint Programming Initiative A healthy diet for a healthy life
  • National Institute for Health and Care Research (FP7/2007–2013, NF-SI-0507-10228, NF-SI-0514-10027)
  • King's College London
  • Israel Science Foundation (FP7/2007-2013)
  • Alberta Innovates
  • Canadian Institutes of Health Research
  • Natural Sciences and Engineering Research Council of Canada (FP7/2007-2013)
  • Medical Research Council (MR/N030125/1, MR/N01183X/1)
  • NIHR Nottingham Biomedical Research Centre
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
  • Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
Keywords
gut microbiota, nutrition, health, diet, probiotics, microbiota modulation
MeSH terms
Gastrointestinal Microbiome, Systematic Reviews as Topic, Humans, Intestinal Absorption, Nutritional Physiological Phenomena, Nutrition Policy, Gastrointestinal Tract, Metabolomics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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