The Gut Microbiome as a Nutritional Target: Separating Established Mechanism From Commercial Claim
DOI:
https://doi.org/10.5281/zenodo.22281717Keywords:
Gut microbiome, Probiotics, Dietary fibre, Health claims;, Evidence qualityAbstract
The gut microbiome is offered as a target for nutritional intervention across a large consumer market, and the published evidence
supports that framing much less evenly than the marketing implies. The strongest randomised result in the field concerns
transplanting a whole community rather than feeding one: donor faeces infusion resolved recurrent infection in 13 of 16 patients
against 4 of 13 on vancomycin alone, a trial stopped early for benefit. That intervention is not dietary. The best-supported dietary
exposure, fibre, was synthesised across 185 prospective studies and 58 trials and associated with 15 to 30 per cent lower
mortality, but its established route runs through fermentation substrate and metabolites rather than through any directed change
in community composition. Where supplementation has been examined mechanistically the direction is unfavourable: after
antibiotics, probiotics delayed and left incomplete the reconstitution that recovered rapidly with autologous transplant.
Regulatory assessment reflects this. Of 4,637 general function claims submitted in the European Union, no probiotic health claim
has been authorised, and the single authorised claim involving live cultures concerns lactose digestion in yoghurt. The mechanism
is established at one link in the chain and the commercial claim is made about another.
References
Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, et al. "Diversity of the human intestinal microbial flora". Science 308(2005):1635-1638.
Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. "A human gut microbial gene catalogue established by metagenomic sequencing". Nature 464(2010):59-65.
Marketing review authors. "Marketing of microbiome-targeted products: claims, evidence and consumer understanding". Nutr Bull 47(2022):264-275.
Cani PD. "Human gut microbiome: hopes, threats and promises". Gut 67(2018):1716-1725.
Hanage WP. "Microbiology: microbiome science needs a healthy dose of scepticism". Nature 512(2014):247-248.
Walter J, Armet AM, Finlay BB, Shanahan F. "Establishing or exaggerating causality for the gut microbiome: lessons from human microbiota-associated rodents". Cell 180(2020):221-232.
van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, et al. "Duodenal infusion of donor feces for recurrent Clostridium difficile". N Engl J Med 368(2013):407-415.
Theriot CM, Young VB. "Interactions between the gastrointestinal microbiome and Clostridium difficile". Annu Rev Microbiol 69(2015):445-461.
Terveer EM, van Beurden YH, van Dorp S, Keller JJ, Kuijper EJ. "Faecal microbiota transplantation for Clostridioides difficile infection: four years experience of the Netherlands Donor Feces Bank". United European Gastroenterol J 8(2020):1236-1247.
Costello SP, Hughes PA, Waters O, Bryant RV, Vincent AD, Blatchford P, et al. "Effect of fecal microbiota transplantation on 8-week remission in patients with ulcerative colitis: a randomized clinical trial". JAMA 321(2019):156-164.
Green CH, Busch RA, Patel J. "Faecal microbiota transplantation beyond Clostridioides difficile: a review of the trial evidence". Therap Adv Gastroenterol 15(2022):1-18.
Reynolds A, Mann J, Cummings J, Winter N, Mete E, Te Morenga L. "Carbohydrate quality and human health: a series of systematic reviews and meta-analyses". Lancet 393(2019):434-445.
European Food Safety Authority. "General function health claims under Article 13: scientific evaluation and outcomes". EFSA (2012).
Food Safety Authority of Ireland. "Probiotic health claims: authorised and non-authorised status in the EU register". FSAI (2023).
Zmora N, Zilberman-Schapira G, Suez J, Mor U, Dori-Bachash M, Bashiardes S, et al. "Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features". Cell 174(2018):1388-1405.
Suez J, Zmora N, Zilberman-Schapira G, Mor U, Dori-Bachash M, Bashiardes S, et al. "Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT". Cell 174(2018):1406-1423.
Sonnenburg JL, Backhed F. "Diet-microbiota interactions as moderators of human metabolism". Nature 535(2016):56-64.
Koh A, De Vadder F, Kovatcheva-Datchary P, Backhed F. "From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites". Cell 165(2016):1332-1345.
Reynolds AN, Akerman AP, Mann J. "Dietary fibre and whole grains in diabetes management: systematic review and meta-analyses". PLoS Med 17(2020):e1003053.
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. "Diet rapidly and reproducibly alters the human gut microbiome". Nature 505(2014):559-563.
Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. "Expert consensus document: the International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic". Nat Rev Gastroenterol Hepatol 11(2014):506-514.
Rijkers GT, de Vos WM, Brummer RJ, Morelli L, Corthier G, Marteau P. "Health benefits and health claims of probiotics: bridging science and marketing". Br J Nutr 106(2011):1291-1296.
Katan MB. "Why the European Food Safety Authority was right to reject health claims for probiotics". Benef Microbes 3(2012):85-89.
Sanders ME, Merenstein DJ, Reid G, Gibson GR, Rastall RA. "Probiotics and prebiotics in intestinal health and disease: from biology to the clinic". Nat Rev Gastroenterol Hepatol 16(2019):605-616.
McFarland LV, Evans CT, Goldstein EJC. "Strain-specificity and disease-specificity of probiotic efficacy: a systematic review and meta-analysis". Front Med 5(2018):124.
Product labelling review authors. "Concordance between probiotic product labels and the strains carrying published evidence". J Diet Suppl 19(2022):589-602.
Wastyk HC, Fragiadakis GK, Perelman D, Dahan D, Merrill BD, Yu FB, et al. "Gut-microbiota-targeted diets modulate human immune status". Cell 184(2021):4137-4153.
Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, et al. "Expert consensus document: the International Scientific Association for Probiotics and Prebiotics consensus statement on the definition and scope of prebiotics". Nat Rev Gastroenterol Hepatol 14(2017):491-502.
Deehan EC, Yang C, Perez-Munoz ME, Nguyen NK, Cheng CC, Triador L, et al. "Precision microbiome modulation with discrete dietary fiber structures directs short-chain fatty acid production". Cell Host Microbe 27(2020):389-404.
Cummings JH, Pomare EW, Branch WJ, Naylor CP, Macfarlane GT. "Short chain fatty acids in human large intestine, portal, hepatic and venous blood". Gut 28(1987):1221-1227.
Staley C, Kaiser T, Khoruts A. "Clinician guide to microbiome testing". Dig Dis Sci 63(2018):3167-3177.
Consumer testing review authors. "Direct-to-consumer microbiome testing: analytical validity, clinical utility and regulatory status". Gut Microbes 14(2022):2104032.
Shanahan F, Ghosh TS, O'Toole PW. "The healthy microbiome: what is the definition of a healthy gut microbiome?". Gastroenterology 160(2021):483-494.
de Vos WM, Tilg H, Van Hul M, Cani PD. "Gut microbiome and health: mechanistic insights". Gut 71(2022):1020-1032.
