Review article: FODMAPS, prebiotics and gut health-the FODMAP hypothesis revisited.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Author(s): Gibson PR;Gibson PR; Halmos EP; Halmos EP; Muir JG; Muir JG
  • Source:
    Alimentary pharmacology & therapeutics [Aliment Pharmacol Ther] 2020 Jul; Vol. 52 (2), pp. 233-246. Date of Electronic Publication: 2020 Jun 20.
  • Publication Type:
    Journal Article; Review
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 8707234 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2036 (Electronic) Linking ISSN: 02692813 NLM ISO Abbreviation: Aliment Pharmacol Ther Subsets: MEDLINE
    • Publication Information:
      Publication: Oxford : Wiley-Blackwell
      Original Publication: [Oxford, OX] : Blackwell Scientific Publications, [c1987-
    • Subject Terms:
    • Abstract:
      Background: Restriction of dietary FODMAP intake can alleviate symptoms in patients with irritable bowel syndrome. Because many FODMAPs have prebiotic actions, there is concern that their dietary restriction leads to dysbiosis with health consequences, and their intake is being encouraged by addition to foods and via supplements.
      Aims: To examine the hazards and benefits of high and low FODMAP intake.
      Methods: Current literature was reviewed and alternative hypotheses formulated.
      Results: Low FODMAP intake reduces abundance of faecal Bifidobacteria without known adverse outcomes and has no effect on diversity, but the reduction in bacterial density may potentially be beneficial to gut health. Supplementary prebiotics can markedly elevate the intake of FODMAPs over levels consumed in the background diet. While this increases the abundance of Bifidobacteria, it adversely affects gut health in animal studies by inducing colonic mucosal barrier dysfunction, mucosal inflammation and visceral hypersensitivity. Rapid colonic fermentation is central to the identified mechanisms that include injury from high luminal concentrations of short-chain fatty acids and low pH, and inflammatory effects of increased endotoxin load and glycation of macromolecules. Whether these observations translate into humans requires further study. Opposing hypotheses are presented whereby excessive intake of FODMAPs might have health benefits via prebiotic effects, but might also be injurious and contribute to the apparent increase in functional intestinal disorders.
      Conclusions: Reduced FODMAP intake has few deleterious effects on gut microbiota. Consequences (both positive and negative) of excessive carbohydrate fermentation in the human intestines from elevated FODMAP intake require more attention.
      (© 2020 John Wiley & Sons Ltd.)
    • References:
      Gibson PR, Shepherd SJ. Personal view: food for thought - western lifestyle and susceptibility to Crohn's disease. The FODMAP hypothesis. Aliment Pharmacol Ther. 2005;21:1399-1409.
      Mitchell H, Porter J, Gibson PR, et al. Review article: implementation of a diet low in FODMAPs for patients with irritable bowel syndrome-directions for future research. Aliment Pharmacol Ther. 2019;49:124-139.
      Halmos EP, Gibson PR. Controversies and reality of the FODMAP diet for patients with irritable bowel syndrome. J Gastroenterol Hepatol. 2019;34:1134-1142.
      Vandenplas Y, Zakharova I, Dmitrieva Y. Oligosaccharides in infant formula: more evidence to validate the role of prebiotics. Br J Nutr. 2015;113:1339-1344.
      Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14:491-502.
      Meyer D, Stasse-Wolthuis M. The bifidogenic effect of inulin and oligofructose and its consequences for gut health. Eur J Clin Nutr. 2009;63:1277-1289.
      Verhoog S, Taneri PE, Roa Díaz ZM, et al. Dietary factors and modulation of bacteria strains of Akkermansia muciniphila and Faecalibacterium prausnitzii: a systematic review. Nutrients. 2019;11:pii: E1565.
      Halmos EP, Christophersen CT, Bird AR, et al. Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut. 2015;64:93-100.
      Halmos EP, Christophersen CT, Bird AR, et al. Consistent prebiotic effect on gut microbiota with altered FODMAP intake in patients with Crohn's disease: a randomised, controlled cross-over trial of well-defined diets. Clin Transl Gastroenterol. 2016;7:e164.
      Wilson B, Rossi M, Dimidi E, et al. Prebiotics in irritable bowel syndrome and other functional bowel disorders in adults: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2019;109:1098-1111.
      Benjamin JL, Hedin CRH, Koutsoumpas A, et al. Randomised, double-blind, placebo-controlled trial of fructo-oligosaccharides in active Crohn's disease. Gut. 2011;60:923-929.
      Vaghef-Mehrabany E, Maleki V, Behrooz M, et al. Can psychobiotics "mood" ify gut? An update systematic review of randomized controlled trials in healthy and clinical subjects, on anti-depressant effects of probiotics, prebiotics, and synbiotics. Clin Nutr. 2020;39:1395-1410.
      Zheng HJ, Guo J, Jia QI, et al. The effect of probiotic and synbiotic supplementation on biomarkers of inflammation and oxidative stress in diabetic patients: a systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2019;142:303-313.
      McFarlane C, Ramos CI, Johnson DW, et al. Prebiotic, probiotic, and synbiotic supplementation in chronic kidney disease: a systematic review and meta-analysis. J Ren Nutr. 2019;29:209-220.
      Shamasbi SG, Ghanbari-Homayi S, Mirghafourvand M. The effect of probiotics, prebiotics, and synbiotics on hormonal and inflammatory indices in women with polycystic ovary syndrome: a systematic review and meta-analysis. Eur J Nutr. 2020;59:433-450.
      McLoughlin RF, Berthon BS, Jensen ME, et al. Short-chain fatty acids, prebiotics, synbiotics, and systemic inflammation: a systematic review and meta-analysis. Am J Clin Nutr. 2017;106:930-945.
      McFarland LV, Goh S. Are probiotics and prebiotics effective in the prevention of travellers' diarrhea: a systematic review and meta-analysis. Travel Med Infect Dis. 2019;27:11-19.
      Jarde A, Lewis-Mikhael A-M, Moayyedi P, et al. Pregnancy outcomes in women taking probiotics or prebiotics: a systematic review and meta-analysis. BMC Pregnancy Childbirth. 2018;18:14.
      Tian X, Pi YP, Liu XL, Chen H, Chen WQ. Supplemented use of pre-, pro-, and synbiotics in severe acute pancreatitis: an updated systematic review and meta-analysis of 13 randomized controlled trials. Front Pharmacol. 2018;9:690.
      Gan Y, Su S, Li B, Fang C. Efficacy of probiotics and prebiotics in prevention of infectious complications following hepatic resections: systematic review and meta-analysis. J Gastrointestin Liver Dis. 2019;28:205-211.
      Ong DK, Mitchell SB, Barrett JS, et al. Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome. J Gastroenterol Hepatol. 2010;25:1366-1373.
      Barrett JS, Gibson PR. Development and validation of a comprehensive semi-quantitative food frequency questionnaire that includes FODMAP intake and glycemic index. J Am Diet Assoc. 2010;110:1469-1476.
      Staudacher HM, Lomer MCE, Farquharson FM, et al. A diet low in FODMAPs reduces symptoms in patients with irritable bowel syndrome and a probiotic restores Bifidobacterium species: a randomized controlled trial. Gastroenterology. 2017;153:936-947.
      Halmos EP, Power VA, Shepherd SJ, et al. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology. 2014;146:67-75.
      Hugenholtz F, de Vos WM. Mouse models for human intestinal microbiota research: a critical evaluation. Cell Mol Life Sci. 2018;75:149-160.
      Kararli TT. Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals. Biopharm Drug Dispos. 1995;16:351-380.
      Cao X, Gibbs ST, Fang L, et al. Why is it challenging to predict intestinal drug absorption and oral bioavailability in human using rat model. Pharm Res. 2006;23:1675-1686.
      Bovee-Oudenhoven IM, ten Bruggencate SJ, Lettink-Wissink ML, et al. Dietary fructo-oligosaccharides and lactulose inhibit intestinal colonisation but stimulate translocation of Salmonella in rats. Gut. 2003;52:1572-1578.
      Petersen A, Heegaard PMH, Pedersen AL, et al. Some putative prebiotics increase the severity of Salmonella enterica serovar Typhimurium infection in mice. BMC Microbiol. 2009;9:245.
      Chen B-R, Du L-J, He H-Q, et al. Fructo-oligosaccharide intensifies visceral hypersensitivity and intestinal inflammation in a stress-induced irritable bowel syndrome mouse model. World J Gastroenterol. 2017;23:8321-8333.
      Kamphuis JBJ, Guiard B, Leveque M, et al. Lactose and fructo-oligosaccharides increase visceral sensitivity in mice via glycation processes, increasing mast cell density in colonic mucosa. Gastroenterology. 2020;158:652-663.
      Hughes R, Rowland IR. Stimulation of apoptosis by two prebiotic chicory fructans in the rat colon. Carcinogenesis. 2001;22:43-47.
      Zhou S-Y, Gillilland M, Wu X, et al. FODMAP diet modulates visceral nociception by lipopolysaccharide-mediated intestinal inflammation and barrier dysfunction. J Clin Invest. 2018;128:267-280.
      Tuck C, De Palma G, Takami K, et al.Experimental reproducibility in preclinical research may be influenced by the nutritional profile of standard rodent chows. Gastroenterology2019;156,S-481.
      Young GP, Folino M, McIntyre A, et al. Wheat bran suppresses potato-starch potentiated tumorigenesis at the aberrant crypt stage in a rat model of colorectal cancer. Gastroenterology. 1996;100:508-514.
      Ten Bruggencate SJM, Bovee-Oudenhoven IMJ, Lettink-Wissink MLG, et al. Dietary fructooligosaccharides affect intestinal barrier function in healthy men. J Nutr. 2006;136:70-74.
      Yao CK, Muir JG, Gibson PR. Review article: insights into colonic protein fermentation, its modulation and potential health implications. Aliment Pharmacol Ther. 2016;43:181-196.
      Hustoft TN, Hausken T, Ystad SO, et al. Effects of varying dietary content of fermentable short-chain carbohydrates on symptoms, fecal microenvironment, and cytokine profiles in patients with irritable bowel syndrome. Neurogastroenterol Motil. 2017;29:e12969.
      Valeur J, Småstuen MC, Knudsen T, et al. Exploring gut microbiota composition as an indicator of clinical response to dietary FODMAP restriction in patients with irritable bowel syndrome. Dig Dis Sci. 2018;63:429-436.
      Loo JV, Cummings J, Delzenne N, et al. Functional food properties of non-digestible oligosaccharides: a consensus report from the ENDO project (DGXII AIRII-CT94-1095). Br J Nutr. 1999;81:121-132.
      Sloan TJ, Jalanka J, Major GAD, et al. A low FODMAP diet is associated with changes in the microbiota and reduction in breath hydrogen but not colonic volume in healthy subjects. PLoS One. 2018;13:e0201410.
      Cox SR, Lindsay JO, Fromentin S, et al. Effects of low FODMAP diet on symptoms, fecal microbiome, and markers of inflammation in patients with quiescent inflammatory bowel disease in a randomized trial. Gastroenterology. 2020;158:176-188.
      McIntosh K, Reed DE, Schneider T, et al. FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial. Gut. 2017;66:1241-1251.
      d’Hennezel E, Abubucker S, Murphy LO, et al. Total lipopolysaccharide from the human gut microbiome silences toll-like receptor signaling. mSystems. 2017;2.
      Staudacher HM, Whelan K, Irving PM, et al. Comparison of symptom response following advice for a diet low in fermentable carbohydrates (FODMAPs) versus standard dietary advice in patients with irritable bowel syndrome. J Hum Nutr Diet. 2011;24:487-495.
      Singh SP, Jadaun JS, Narnoliya LK, et al. Prebiotic oligosaccharides: special focus on fructooligosaccharides, its biosynthesis and bioactivity. Appl Biochem Biotechnol. 2017;183:613-635.
      Vandeputte D, Falony G, Vieira-Silva S, et al. Prebiotic inulin-type fructans induce specific changes in the human gut microbiota. Gut. 2017;66:1968-1974.
      Dewulf EM, Cani PD, Claus SP, et al. Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. Gut. 2013;62:1112-1121.
      Baron EJ. Bilophila wadsworthia: a unique Gram-negative anaerobic rod. Anaerobe. 1997;3:83-86.
      David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559-563.
      Huaman J-W, Mego M, Manichanh C, et al. Effects of prebiotics vs a diet low in FODMAPs in patients with functional gut disorders. Gastroenterology. 2018;155:1004-1007.
      da Silva SM, Venceslau SS, Fernandes CLV, et al. Hydrogen as an energy source for the human pathogen Bilophila wadsworthia. Antonie Van Leeuwenhoek. 2008;93:381-390.
      Rowland I, Gibson G, Heinken A, et al. Gut microbiota functions: metabolism of nutrients and other food components. Eur J Nutr. 2018;57:1-24.
      Kalantar-Zadeh K, Berean KJ, Burgell RE, et al. Intestinal gases: influence on gut disorders and the role of dietary manipulations. Nat Rev Gastroenterol Hepatol. 2019;16:733-747.
      Gill PA, van Zelm MC, Muir JG, et al. Review article: short chain fatty acids as potential therapeutic agents in human gastrointestinal and inflammatory disorders. Aliment Pharmacol Ther. 2018;48:15-34.
      Whisner CM, Castillo LF. Prebiotics, bone and mineral metabolism. Calcif Tissue Int. 2018;102:443-479.
      Cashman K. Prebiotics and calcium bioavailability. Curr Issues Intest Microbiol. 2003;4:21-32.
      Duncan SH, Louis P, Thomson JM, et al. The role of pH in determining the species composition of the human colonic microbiota. Environ Microbiol. 2009;11:2112-2122.
      Perman JA, Modler S, Olson AC. Role of pH in production of hydrogen from carbohydrates by colonic bacterial flora. Studies in vivo and in vitro. J Clin Invest. 1981;67:643-650.
      Argenzio RA, Meuten DJ. Short-chain fatty acids induce reversible injury of porcine colon. Dig Dis Sci. 1991;36:1459-1468.
      Farmer AD, Mohammed SD, Dukes GE, et al. Caecal pH is a biomarker of excessive colonic fermentation. World J Gastroenterol. 2014;20:5000-5007.
      McIntyre A, Young GP, Taranto T, et al. Different fibers have different regional effects on luminal contents of rat colon. Gastroenterology. 1991;101:1274-1281.
      Govers M, Gannon NJ, Dunshea FR, et al. Wheat bran affects the site of fermentation of resistant starch and luminal indexes related to colon cancer risk: a study in pigs. Gut. 1999;45:840-847.
      Eswaran S, Muir J, Chey WD. Fiber and functional gastrointestinal disorders. Am J Gastroenterol. 2013;108:718-727.
      Harvie RM, Chisholm AW, Bisanz JE, et al. Long-term irritable bowel syndrome symptom control with reintroduction of selected FODMAPs. World J Gastroenterol. 2017;23:4632-4643.
      Saunders DR, Sillery J. Effect of lactate and H1 on structure and function of rat intestine. Dig Dis Sci. 1982;27:33-41.
      Windey K, De Preter V, Verbeke K. Relevance of protein fermentation to gut health. Mol Nutr Food Res. 2012;56:184-196.
      Yao CK, Rotbart A, Ou JZ, Kalantar-Zadeh K, Muir JG, Gibson PR. Modulation of colonic hydrogen sulfide production by diet and mesalazine utilizing a novel gas-profiling technology. Gut Microbes. 2018;9:510-522.
      Wallace JL, Motta JP, Buret AG. Hydrogen sulfide: an agent of stability at the microbiome-mucosa interface. Am J Physiol Gastrointest Liver Physiol. 2018;314:G143-G149.
      Roediger WEW. Review article: nitric oxide from dysbiotic bacterial respiration of nitrate in the pathogenesis and as a target for therapy of ulcerative colitis. Aliment Pharmacol Ther. 2008;27:531-541.
      Matsunami M, Tarui T, Mitani K, et al. Luminal hydrogen sulfide plays a pronociceptive role in mouse colon. Gut. 2009;58:751-761.
      Ohge H, Furne JK, Springfield J, et al. Association between fecal hydrogen sulfide production and pouchitis. Dis Colon Rectum. 2005;48:469-475.
      Gerber T, Schomerus H. Hepatic encephalopathy in liver cirrhosis: pathogenesis, diagnosis and management. Drugs. 2000;60:1353-1370.
      Chatterjee S, Park S, Low K, et al. The degree of breath methane production in IBS correlates with the severity of constipation. Am J Gastroenterol. 2007;102:837-841.
      Li HE, Wang Y-J, Wang S-R, et al. Comments and hypotheses on the mechanism of methane against ischemia/reperfusion injury. Med Gas Res. 2017;7:120-123.
      Ohta S. Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine. Pharmacol Ther. 2014;144:1-11.
      Slezák J, Kura B, Frimmel K, et al. Preventive and therapeutic application of molecular hydrogen in situations with excessive production of free radicals. Physiol Res. 2016;65(Suppl 1):S11-28.
      Aggio RBM, White P, Jayasena H, et al. Irritable bowel syndrome and active inflammatory bowel disease diagnosed by faecal gas analysis. Aliment Pharmacol Ther. 2017;45:82-90.
      Bosch S, Berkhout DJ, Ben Larbi I, et al. Fecal volatile organic compounds for early detection of colorectal cancer: where are we now? J Cancer Res Clin Oncol. 2019;145:223-234.
      Rossi M, Aggio R, Staudacher HM, et al. Volatile organic compounds in feces associate with response to dietary intervention in patients with irritable bowel syndrome. Clin Gastroenterol Hepatol. 2018;16:385-391.
      Ten Bruggencate SJM, Bovee-Oudenhoven IMJ, Lettink-Wissink MLG, et al. Dietary fructo-oligosaccharides dose-dependently increase translocation of Salmonella in rats. J Nutr. 2003;133:2313-2318.
      Ten Bruggencate SJ, Bovee-Oudenhoven IM, Lettink-Wissink ML, et al. Dietary fructo-oligosaccharides and inulin decrease resistance of rats to Salmonella: protective role of calcium. Gut. 2004;53:530-535.
      Remesy C, Levrat MA, Gamet L, et al. Cecal fermentations in rats fed oligosaccharides (inulin) are modulated by dietary calcium level. Am J Physiol. 1993;264(5 Pt 1):G855-G862.
      Guarner F. Studies with inulin-type fructans on intestinal infections, permeability, and inflammation. J Nutr. 2568S;137:2568S-2571S.
      Singh V, Yeoh BS, Walker RE, et al. Microbiota fermentation-NLRP3 axis shapes the impact of dietary fibres on intestinal inflammation. Gut. 2019;68:1801-1812.
      Rhodes JM. Nutrition and gut health: the impact of specific dietary components - it's not just five-a-day. Proc Nutr Soc. 2020;1-10.
      Roediger WE, Heyworth M, Willoughby P, et al. Luminal ions and short chain fatty acids as markers of functional activity of the mucosa in ulcerative colitis. J Clin Pathol. 1982;35:323-326.
      Gibson PR, Nov R, Fielding M, et al. The relationship of hydrolase activities to epithelial cell turnover in distal colonic mucosa of normal rats. J Gastroenterol Hepatol. 1999;14:866-872.
      Gibson PR. Use of the low-FODMAP diet in inflammatory bowel disease. J Gastroenterol Hepatol. 2017;32(Suppl 1):40-42.
      Cox SR, Prince AC, Myers CE, et al. Fermentable carbohydrates [FODMAPs] exacerbate functional gastrointestinal symptoms in patients with inflammatory bowel disease: a randomised, double-blind, placebo-controlled, cross-over, re-challenge trial. J Crohns Colitis. 2017;11:1420-1429.
      Lindsay JO, Whelan K, Stagg AJ, et al. Clinical, microbiological, and immunological effects of fructo-oligosaccharide in patients with Crohn's disease. Gut. 2006;55:348-355.
      Ajamian M, Rosella G, Newnham ED, et al. Assessment of intestinal barrier integrity in non-coeliac wheat sensitivity/irritable bowel syndrome. In: Investigating Markers of Intestinal Barrier Dysfunction in Gastrointestinal Diseases. Monash University Thesis20197:135-155.
      Gibson PR, Burgell RE. Illuminating dark depths. Science. 2018;360:856-857.
      Berean KJ, Ha N, Ou JZ, et al. The safety and sensitivity of a telemetric capsule to monitor gastrointestinal hydrogen production in vivo in healthy subjects: a pilot trial comparison to concurrent breath analysis. Aliment Pharmacol Ther. 2018;48:646-654.
    • Accession Number:
      0 (Monosaccharides)
      0 (Polysaccharides)
    • Publication Date:
      Date Created: 20200621 Date Completed: 20201109 Latest Revision: 20211204
    • Publication Date:
      20231215
    • Accession Number:
      10.1111/apt.15818
    • Accession Number:
      32562590