Microbiome and Its Role in Irritable Bowel Syndrome

Abstract

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.

Fig. 1

References

  1. 1.

    Choung RS, Locke GR 3rd. Epidemiology of IBS. Gastroenterol Clin N Am. 2011;40:1–10.

    Google Scholar 

  2. 2.

    The Burden of Gasterointestinal Diseases. Bethesda, MD: American Gastroenterological Association; 2001.

  3. 3.

    Drossman DA, Camilleri M, Mayer EA, Whitehead WE. AGA technical review on irritable bowel syndrome. Gastroenterology. 2002;123:2108–2131.

    PubMed  Google Scholar 

  4. 4.

    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.

    CAS  PubMed  Google Scholar 

  5. 5.

    McKendrick MW, Read NW. Irritable bowel syndrome–post salmonella infection. J Infect. 1994;29:1–3.

    CAS  PubMed  Google Scholar 

  6. 6.

    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.

    PubMed  PubMed Central  Google Scholar 

  7. 7.

    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.

    PubMed  Google Scholar 

  8. 8.

    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.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    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.

    CAS  PubMed  Google Scholar 

  10. 10.

    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.

    CAS  PubMed  Google Scholar 

  11. 11.

    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.

    CAS  PubMed  Google Scholar 

  12. 12.

    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.

    Article  PubMed  Google Scholar 

  13. 13.

    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.

    CAS  PubMed  Google Scholar 

  14. 14.

    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.

    CAS  PubMed  Google Scholar 

  15. 15.

    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.

    Article  PubMed  Google Scholar 

  16. 16.

    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.

    PubMed  PubMed Central  Google Scholar 

  17. 17.

    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.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    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.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    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.

    PubMed  PubMed Central  Google Scholar 

  20. 20.

    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.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    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.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    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.

    CAS  PubMed  Google Scholar 

  23. 23.

    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.

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Chira A, Dumitrascu DL. Serum biomarkers for irritable bowel syndrome. Clujul Med. 2015;88:258–264.

    PubMed  PubMed Central  Google Scholar 

  25. 25.

    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.

    CAS  PubMed  Google Scholar 

  26. 26.

    Pike BL, Paden KA, Alcala AN, et al. Immunological biomarkers in postinfectious irritable bowel syndrome. J Travel Med. 2015;22:242–250.

    PubMed  Google Scholar 

  27. 27.

    Maxwell PR, Rink E, Kumar D, Mendall MA. Antibiotics increase functional abdominal symptoms. Am J Gastroenterol. 2002;97:104.

    CAS  PubMed  Google Scholar 

  28. 28.

    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.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    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.

    Article  PubMed  Google Scholar 

  30. 30.

    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.

    Google Scholar 

  31. 31.

    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.

    PubMed  Google Scholar 

  32. 32.

    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.

    PubMed  Google Scholar 

  33. 33.

    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.

    PubMed  Google Scholar 

  34. 34.

    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.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    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.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    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.

    CAS  PubMed  Google Scholar 

  37. 37.

    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.

    CAS  PubMed  Google Scholar 

  38. 38.

    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.

    PubMed  Google Scholar 

  39. 39.

    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.

    CAS  PubMed  Google Scholar 

  40. 40.

    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.

    CAS  PubMed  Google Scholar 

  41. 41.

    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.

    CAS  PubMed  Google Scholar 

  42. 42.

    Ringel Y. The gut microbiome in irritable bowel syndrome and other functional bowel disorders. Gastroenterol Clin N Am. 2017;46:91–101.

    Google Scholar 

  43. 43.

    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.

    Article  PubMed  Google Scholar 

  44. 44.

    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.

    PubMed  Google Scholar 

  45. 45.

    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.

    Article  PubMed  Google Scholar 

  46. 46.

    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.

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    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.

    CAS  PubMed  Google Scholar 

  48. 48.

    Miller TL, Wolin MJ. Enumeration of Methanobrevibacter smithii in human feces. Arch Microbiol. 1982;131:14–18.

    CAS  PubMed  Google Scholar 

  49. 49.

    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.

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    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.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Raskov H, Burcharth J, Pommergaard HC, Rosenberg J. Irritable bowel syndrome, the microbiota and the gut–brain axis. Gut Microbes. 2016;7:365–383.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    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.

    PubMed  Google Scholar 

  53. 53.

    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.

    CAS  PubMed  Google Scholar 

  54. 54.

    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.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55.

    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.

    PubMed Central  Google Scholar 

  56. 56.

    Wouters MM, Vicario M, Santos J. The role of mast cells in functional GI disorders. Gut. 2016;65:155–168.

    CAS  Google Scholar 

  57. 57.

    Yano JM, Yu K, Donaldson GP, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161:264–276.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Foster JA, Rinaman L, Cryan JF. Stress and the gut–brain axis: regulation by the microbiome. Neurobiol Stress. 2017;7:124–136.

    PubMed  PubMed Central  Google Scholar 

  59. 59.

    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.

    PubMed  Google Scholar 

  60. 60.

    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.

    PubMed  PubMed Central  Google Scholar 

  61. 61.

    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.

    CAS  PubMed  Google Scholar 

  62. 62.

    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.

    PubMed  Google Scholar 

  63. 63.

    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.

    CAS  PubMed  Google Scholar 

  64. 64.

    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.

    CAS  PubMed  Google Scholar 

  65. 65.

    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.

    CAS  PubMed  Google Scholar 

  66. 66.

    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.

    CAS  Article  PubMed  Google Scholar 

  67. 67.

    Borowiec AM, Fedorak RN. The role of probiotics in management of irritable bowel syndrome. Curr Gastroenterol Rep. 2007;9:393–400.

    PubMed  Google Scholar 

  68. 68.

    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.

    PubMed  PubMed Central  Google Scholar 

  69. 69.

    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.

    PubMed  Google Scholar 

  70. 70.

    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.

    PubMed  Google Scholar 

  71. 71.

    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.

    PubMed  Google Scholar 

  72. 72.

    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.

    CAS  PubMed  Google Scholar 

  73. 73.

    Altobelli E, Del Negro V, Angeletti PM, Latella G. Low-FODMAP diet improves irritable bowel syndrome symptoms: a meta-analysis. Nutrients. 2017;9:940.

    PubMed Central  Google Scholar 

  74. 74.

    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.

    CAS  PubMed  Google Scholar 

  75. 75.

    Hill P, Muir JG, Gibson PR. Controversies and recent developments of the low-FODMAP diet. Gastroenterol Hepatol NY. 2017;13:36–45.

    Google Scholar 

  76. 76.

    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.

    PubMed  Google Scholar 

  77. 77.

    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.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78.

    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.

    PubMed  PubMed Central  Google Scholar 

  79. 79.

    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.

    PubMed  Google Scholar 

  80. 80.

    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.

    CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Mark Pimentel.

Ethics declarations

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.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

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

Download citation

Keywords

  • Irritable bowel syndrome
  • Gut microbiome
  • Acute gastroenteritis
  • Small intestinal bacterial overgrowth
  • Brain-gut axis
  • Diet
  • Antibiotics