Irritable bowel syndrome (IBS) is an extremely common and often very debilitating chronic functional gastrointestinal disorder. Despite its prevalence, significant associated healthcare costs, and quality-of-life issues for affected individuals, our understanding of its etiology remained limited. However, it is now evident that microbial factors play key roles in IBS pathophysiology. Acute gastroenteritis following exposure to pathogens can precipitate the development of IBS, and studies have demonstrated changes in the gut microbiome in IBS patients. These changes may explain some of the symptoms of IBS, including visceral hypersensitivity, as gut microbes exert effects on the host immune system and gut barrier function, as well as the brain–gut axis. Microbial differences also appear to underlie the two main functional categories of IBS: diarrhea-predominant IBS (IBS-D) is associated with small intestinal bacterial overgrowth, which can be diagnosed by a positive hydrogen breath test, and constipation-predominant IBS (IBS-C) is associated with increased levels of methanogenic archaea, which can be diagnosed by a positive methane breath test. Mechanistically, the pathogens that cause gastroenteritis and trigger subsequent IBS development produce a common toxin, cytolethal distending toxin B (CdtB), and antibodies raised against CdtB cross-react with the cytoskeletal protein vinculin and impair gut motility, facilitating bacterial overgrowth. In contrast, methane gas slows intestinal contractility, which may facilitate the development of constipation. While antibiotics and dietary manipulations have been used to relieve IBS symptoms, with varying success, elucidating the specific mechanisms by which gut microbes exert their effects on the host may allow the development of targeted treatments that may successfully treat the underlying causes of IBS.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Choung RS, Locke GR 3rd. Epidemiology of IBS. Gastroenterol Clin N Am. 2011;40:1–10.
The Burden of Gasterointestinal Diseases. Bethesda, MD: American Gastroenterological Association; 2001.
Drossman DA, Camilleri M, Mayer EA, Whitehead WE. AGA technical review on irritable bowel syndrome. Gastroenterology. 2002;123:2108–2131.
Chaudhary NA, Truelove SC. The irritable colon syndrome. A study of the clinical features, predisposing causes, and prognosis in 130 cases. Q J Med. 1962;31:307–322.
McKendrick MW, Read NW. Irritable bowel syndrome–post salmonella infection. J Infect. 1994;29:1–3.
Klem F, Wadhwa A, Prokop LJ, et al. Prevalence, risk factors, and outcomes of irritable bowel syndrome after infectious enteritis: a systematic review and meta-analysis. Gastroenterology. 2017;152:1042–1054.e1.
Goodsall TM, Talley NJ, Rassam L, et al. Unique pathology of colonic spirochaetosis characterised by mucosal eosinophilia is linked to diarrhoea and IBS. Gut. 2017;66:978.
Bonfiglio F, Zheng T, Garcia-Etxebarria K, et al. Female-specific association between variants on chromosome 9 and self-reported diagnosis of irritable bowel syndrome. Gastroenterology. 2018;155:168–179.
Sibelli A, Chalder T, Everitt H, Workman P, Windgassen S, Moss-Morris R. A systematic review with meta-analysis of the role of anxiety and depression in irritable bowel syndrome onset. Psychol Med. 2016;46:3065–3080.
Spreadbury I, Ochoa-Cortes F, Ibeakanma C, Martin N, Hurlbut D, Vanner SJ. Concurrent psychological stress and infectious colitis is key to sustaining enhanced peripheral sensory signaling. Neurogastroenterol Motil. 2015;27:347–355.
Murakami T, Kamada K, Mizushima K, et al. Changes in intestinal motility and gut microbiota composition in a rat stress model. Digestion. 2017;95:55–60.
Porter CK, Gloor K, Cash BD, Riddle MS. Risk of functional gastrointestinal disorders in U.S. military following self-reported diarrhea and vomiting during deployment. Dig Dis Sci. 2011;56:3262–3269. https://doi.org/10.1007/s10620-011-1762-3.
Koloski NA, Jones M, Talley NJ. Evidence that independent gut-to-brain and brain-to-gut pathways operate in the irritable bowel syndrome and functional dyspepsia: a 1-year population-based prospective study. Aliment Pharmacol Ther. 2016;44:592–600.
Akiho H, Deng Y, Blennerhassett P, Kanbayashi H, Collins SM. Mechanisms underlying the maintenance of muscle hypercontractility in a model of postinfective gut dysfunction. Gastroenterology. 2005;129:131–141.
Pimentel M, Chatterjee S, Chang C, et al. A new rat model links two contemporary theories in irritable bowel syndrome. Dig Dis Sci. 2008;53:982–989. https://doi.org/10.1007/s10620-007-9977-z.
Jee SR, Morales W, Low K, et al. ICC density predicts bacterial overgrowth in a rat model of post-infectious IBS. World J Gastroenterol. 2010;16:3680–3686.
Spiller RC, Jenkins D, Thornley JP, et al. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut. 2000;47:804–811.
Pimentel M, Soffer EE, Chow EJ, Kong Y, Lin HC. Lower frequency of MMC is found in IBS subjects with abnormal lactulose breath test, suggesting bacterial overgrowth. Dig Dis Sci. 2002;47:2639–2643. https://doi.org/10.1023/A:1021039032413.
Pokkunuri V, Pimentel M, Morales W, et al. Role of cytolethal distending toxin in altered stool form and bowel phenotypes in a rat model of post-infectious irritable bowel syndrome. J Neurogastroenterol Motil. 2012;18:434–442.
Pimentel M, Morales W, Pokkunuri V, et al. Autoimmunity links vinculin to the pathophysiology of chronic functional bowel changes following campylobacter jejuni infection in a rat model. Dig Dis Sci. 2015;60:1195–1205. https://doi.org/10.1007/s10620-014-3435-5.
Shen K, Tolbert CE, Guilluy C, et al. The vinculin C-terminal hairpin mediates F-actin bundle formation, focal adhesion, and cell mechanical properties. J Biol Chem. 2011;286:45103–45115.
Ford AC, Talley NJ, Walker MM, Jones MP. Increased prevalence of autoimmune diseases in functional gastrointestinal disorders: case-control study of 23471 primary care patients. Aliment Pharmacol Ther. 2014;40:827–834.
Pimentel M, Morales W, Rezaie A, et al. Development and validation of a biomarker for diarrhea-predominant irritable bowel syndrome in human subjects. PLoS One. 2015;10:e0126438.
Chira A, Dumitrascu DL. Serum biomarkers for irritable bowel syndrome. Clujul Med. 2015;88:258–264.
Schmulson M, Balbuena R, Corona de Law C. Clinical experience with the use of anti-CdtB and anti-vinculin antibodies in patients with diarrhea in Mexico. Rev Gastroenterol Mex. 2016;81:236–239.
Pike BL, Paden KA, Alcala AN, et al. Immunological biomarkers in postinfectious irritable bowel syndrome. J Travel Med. 2015;22:242–250.
Maxwell PR, Rink E, Kumar D, Mendall MA. Antibiotics increase functional abdominal symptoms. Am J Gastroenterol. 2002;97:104.
Paula H, Grover M, Halder SL, et al. Non-enteric infections, antibiotic use, and risk of development of functional gastrointestinal disorders. Neurogastroenterol Motil. 2015;27:1580–1586.
Codling C, O’Mahony L, Shanahan F, Quigley EM, Marchesi JR. A molecular analysis of fecal and mucosal bacterial communities in irritable bowel syndrome. Dig Dis Sci. 2010;55:392–397. https://doi.org/10.1007/s10620-009-0934-x.
Carroll IM, Ringel-Kulka T, Siddle JP, Ringel Y. Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil. 2012;24:521–530, e248.
Jeffery IB, O’Toole PW, Ohman L, et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut. 2012;61:997–1006.
Ng SC, Lam EF, Lam TT, et al. Effect of probiotic bacteria on the intestinal microbiota in irritable bowel syndrome. J Gastroenterol Hepatol. 2013;28:1624–1631.
Giamarellos-Bourboulis E, Tang J, Pyleris E, et al. Molecular assessment of differences in the duodenal microbiome in subjects with irritable bowel syndrome. Scand J Gastroenterol. 2015;50:1076–1087.
Maharshak N, Ringel Y, Katibian D, et al. Fecal and mucosa-associated intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Dig Dis Sci. 2018;63:1890–1899. https://doi.org/10.1007/s10620-018-5086-4.
Ponnusamy K, Choi JN, Kim J, Lee SY, Lee CH. Microbial community and metabolomic comparison of irritable bowel syndrome faeces. J Med Microbiol. 2011;60:817–827.
Rajilic-Stojanovic M, Biagi E, Heilig HG, et al. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology. 2011;141:1792–1801.
Liu HN, Wu H, Chen YZ, Chen YJ, Shen XZ, Liu TT. Altered molecular signature of intestinal microbiota in irritable bowel syndrome patients compared with healthy controls: a systematic review and meta-analysis. Dig Liver Dis. 2017;49:331–337.
Tap J, Derrien M, Tornblom H, et al. Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology. 2017;152:111–123 e8.
Crouzet L, Gaultier E, Del’Homme C, et al. The hypersensitivity to colonic distension of IBS patients can be transferred to rats through their fecal microbiota. Neurogastroenterol Motil. 2013;25:e272–e282.
Brint EK, MacSharry J, Fanning A, Shanahan F, Quigley EM. Differential expression of toll-like receptors in patients with irritable bowel syndrome. Am J Gastroenterol. 2011;106:329–336.
McKernan DP, Gaszner G, Quigley EM, Cryan JF, Dinan TG. Altered peripheral toll-like receptor responses in the irritable bowel syndrome. Aliment Pharmacol Ther. 2011;33:1045–1052.
Ringel Y. The gut microbiome in irritable bowel syndrome and other functional bowel disorders. Gastroenterol Clin N Am. 2017;46:91–101.
Shah ED, Basseri RJ, Chong K, Pimentel M. Abnormal breath testing in IBS: a meta-analysis. Dig Dis Sci. 2010;55:2441–2449. https://doi.org/10.1007/s10620-010-1276-4.
Posserud I, Stotzer PO, Bjornsson ES, Abrahamsson H, Simren M. Small intestinal bacterial overgrowth in patients with irritable bowel syndrome. Gut. 2007;56:802–808.
Pyleris E, Giamarellos-Bourboulis EJ, Tzivras D, Koussoulas V, Barbatzas C, Pimentel M. The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Dig Dis Sci. 2012;57:1321–1329. https://doi.org/10.1007/s10620-012-2033-7.
Kunkel D, Basseri RJ, Makhani MD, Chong K, Chang C, Pimentel M. Methane on breath testing is associated with constipation: a systematic review and meta-analysis. Dig Dis Sci. 2011;56:1612–1618. https://doi.org/10.1007/s10620-011-1590-5.
Pimentel M, Lin HC, Enayati P, et al. Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile activity. Am J Physiol Gastrointest Liver Physiol. 2006;290:G1089–G1095.
Miller TL, Wolin MJ. Enumeration of Methanobrevibacter smithii in human feces. Arch Microbiol. 1982;131:14–18.
Pimentel M, Chang C, Chua KS, et al. Antibiotic treatment of constipation-predominant irritable bowel syndrome. Dig Dis Sci. 2014;59:1278–1285. https://doi.org/10.1007/s10620-014-3157-8.
Rezaie A, Buresi M, Lembo A, et al. Hydrogen and methane-based breath testing in gastrointestinal disorders: the North American consensus. Am J Gastroenterol. 2017;112:775–784.
Raskov H, Burcharth J, Pommergaard HC, Rosenberg J. Irritable bowel syndrome, the microbiota and the gut–brain axis. Gut Microbes. 2016;7:365–383.
Bhattarai Y, Muniz Pedrogo DA, Kashyap PC. Irritable bowel syndrome: a gut microbiota-related disorder? Am J Physiol Gastrointest Liver Physiol. 2017;312:G52–G62.
Dlugosz A, Nowak P, D’Amato M, et al. Increased serum levels of lipopolysaccharide and antiflagellin antibodies in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil. 2015;27:1747–1754.
Mikkelsen HB. Interstitial cells of Cajal, macrophages and mast cells in the gut musculature: morphology, distribution, spatial and possible functional interactions. J Cell Mol Med. 2010;14:818–832.
Anitha M, Vijay-Kumar M, Sitaraman SV, Gewirtz AT, Srinivasan S. Gut microbial products regulate murine gastrointestinal motility via toll-like receptor 4 signaling. Gastroenterology. 2012;143:1006–1016.e4.
Wouters MM, Vicario M, Santos J. The role of mast cells in functional GI disorders. Gut. 2016;65:155–168.
Yano JM, Yu K, Donaldson GP, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161:264–276.
Foster JA, Rinaman L, Cryan JF. Stress and the gut–brain axis: regulation by the microbiome. Neurobiol Stress. 2017;7:124–136.
De Palma G, Lynch MDJ, Lu J, et al. Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice. Sci Transl Med. 2017;9:eaaf6397.
Labus JS, Hollister EB, Jacobs J, et al. Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome. Microbiome. 2017;5:49.
Ghoshal UC, Srivastava D, Misra A, Ghoshal U. A proof-of-concept study showing antibiotics to be more effective in irritable bowel syndrome with than without small-intestinal bacterial overgrowth: a randomized, double-blind, placebo-controlled trial. Eur J Gastroenterol Hepatol. 2016;28:281–289.
Pimentel M, Chow EJ, Lin HC. Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. A double-blind, randomized, placebo-controlled study. Am J Gastroenterol. 2003;98:412–419.
Pimentel M, Lembo A, Chey WD, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364:22–32.
Lembo A, Pimentel M, Rao SS, et al. Repeat treatment with rifaximin is safe and effective in patients with diarrhea-predominant irritable bowel syndrome. Gastroenterology. 2016;151:1113–1121.
Menees SB, Maneerattannaporn M, Kim HM, Chey WD. The efficacy and safety of rifaximin for the irritable bowel syndrome: a systematic review and meta-analysis. Am J Gastroenterol. 2012;107:28–35.
Kim MS, Morales W, Hani AA, et al. The effect of rifaximin on gut flora and Staphylococcus resistance. Dig Dis Sci. 2013;58:1676–1682. https://doi.org/10.1007/s10620-013-2675-0.
Borowiec AM, Fedorak RN. The role of probiotics in management of irritable bowel syndrome. Curr Gastroenterol Rep. 2007;9:393–400.
Didari T, Mozaffari S, Nikfar S, Abdollahi M. Effectiveness of probiotics in irritable bowel syndrome: updated systematic review with meta-analysis. World J Gastroenterol. 2015;21:3072–3084.
O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128:541–551.
Ki Cha B, Mun Jung S, Hwan Choi C, et al. The effect of a multispecies probiotic mixture on the symptoms and fecal microbiota in diarrhea-dominant irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Clin Gastroenterol. 2012;46:220–227.
Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology. 2014;146:67–75.e5.
Shepherd SJ, Parker FC, Muir JG, Gibson PR. Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence. Clin Gastroenterol Hepatol. 2008;6:765–771.
Altobelli E, Del Negro V, Angeletti PM, Latella G. Low-FODMAP diet improves irritable bowel syndrome symptoms: a meta-analysis. Nutrients. 2017;9:940.
Eswaran SL, Chey WD, Han-Markey T, Ball S, Jackson K. A randomized controlled trial comparing the low FODMAP diet vs modified NICE guidelines in US adults with IBS-D. Am J Gastroenterol. 2016;111:1824–1832.
Hill P, Muir JG, Gibson PR. Controversies and recent developments of the low-FODMAP diet. Gastroenterol Hepatol NY. 2017;13:36–45.
Johnsen PH, Hilpüsch F, Cavanagh JP, et al. Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single-centre trial. Lancet Gastroenterol Hepatol. 2018;3:17–24.
Halkjaer SI, Christensen AH, Lo BZS, et al. Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study. Gut. 2018;67:2107–2115.
Kerckhoffs AP, Samsom M, van der Rest ME, et al. Lower Bifidobacteria counts in both duodenal mucosa-associated and fecal microbiota in irritable bowel syndrome patients. World J Gastroenterol. 2009;15:2887–2892.
Kerckhoffs AP, Ben-Amor K, Samsom M, et al. Molecular analysis of faecal and duodenal samples reveals significantly higher prevalence and numbers of Pseudomonas aeruginosa in irritable bowel syndrome. J Med Microbiol. 2011;60:236–245.
Rangel I, Sundin J, Fuentes S, et al. The relationship between faecal-associated and mucosal-associated microbiota in irritable bowel syndrome patients and healthy subjects. Aliment Pharmacol Ther 2015;42:1211–1221.
Conflict of interest
MP is a consultant for and has received grant support from Salix Pharmaceuticals. MP also consults for US Medical and Shire. MP has equity in and consults for Gemelli Biotech, Naia Pharmaceuticals, and Synthetic Biologics. Cedars-Sinai has licensing agreements with Bausch Health, Naia Pharmaceuticals, Synthetic Biologics and Gemelli Biotech. AL has served on the advisory boards for Allergen, Salix Pharmaceuticals, Valeant Pharmaceuticals, Alkermes, Arena, Aoen Biopharma, Takeda, Bioamerica and Ironwood Pharmaceuticals.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Pimentel, M., Lembo, A. Microbiome and Its Role in Irritable Bowel Syndrome. Dig Dis Sci 65, 829–839 (2020). https://doi.org/10.1007/s10620-020-06109-5
- Irritable bowel syndrome
- Gut microbiome
- Acute gastroenteritis
- Small intestinal bacterial overgrowth
- Brain-gut axis