Download PDF
Clin Colon Rectal Surg 2023; 36(02): 120-126
DOI: 10.1055/s-0042-1760680
Review Article

The Role of the Microbiome in the Etiology of Inflammatory Bowel Diseases

Ariel Halper-Stromberg
1   University of Chicago Medicine Inflammatory Bowel Disease Center, Dept of Medicine, Chicago, Illinois
,
Sushila R. Dalal
1   University of Chicago Medicine Inflammatory Bowel Disease Center, Dept of Medicine, Chicago, Illinois
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Inflammatory bowel diseases (IBDs) result from dysregulated immune responses to environmental and microbial triggers in genetically susceptible hosts. Many clinical observations and animal studies support the role of the microbiome in the pathogenesis of IBD. Restoration of the fecal stream leads to postoperative Crohn's recurrence, while diversion can treat active inflammation. Antibiotics can be effective in prevention of postoperative Crohn's recurrence and in pouch inflammation. Several gene mutations associated with Crohn's risk lead to functional changes in microbial sensing and handling. However, the evidence linking the microbiome to the IBD is largely correlative, given the difficulty in studying the microbiome before disease occurs. Attempts to modify the microbial triggers of inflammation have had modest success to date. Exclusive enteral nutrition can treat Crohn's inflammation though no whole food diet to date has been shown to treat inflammation. Manipulation of the microbiome through fecal microbiota transplant and probiotics have had limited success. Further focus on early changes in the microbiome and functional consequences of microbial changes through the study of metabolomics are needed to help advance the field.

Keywords

inflammatory bowel disease - microbiome - Crohn's disease - ulcerative colitis


Publication History

Article published online:
25 January 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Singh S, Ding NS, Mathis KL. et al. Systematic review with meta-analysis: faecal diversion for management of perianal Crohn's disease. Aliment Pharmacol Ther 2015; 42 (07) 783-792
    CrossrefPubMedGoogle Scholar
  • 2 Harper PH, Truelove SC, Lee EC, Kettlewell MG, Jewell DP. Split ileostomy and ileocolostomy for Crohn's disease of the colon and ulcerative colitis: a 20 year survey. Gut 1983; 24 (02) 106-113
    CrossrefPubMedGoogle Scholar
  • 3 Rutgeerts P, Goboes K, Peeters M. et al. Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum. Lancet 1991; 338 (8770): 771-774
    CrossrefPubMedGoogle Scholar
  • 4 D'Haens GR, Geboes K, Peeters M, Baert F, Penninckx F, Rutgeerts P. Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology 1998; 114 (02) 262-267
    CrossrefPubMedGoogle Scholar
  • 5 Doherty GA, Bennett GC, Cheifetz AS, Moss AC. Meta-analysis: targeting the intestinal microbiota in prophylaxis for post-operative Crohn's disease. Aliment Pharmacol Ther 2010; 31 (08) 802-809
    CrossrefPubMedGoogle Scholar
  • 6 Glick LR, Sossenheimer PH, Ollech JE. et al. Low-dose metronidazole is associated with a decreased rate of endoscopic recurrence of Crohn's disease after ileal resection: a retrospective cohort study. J Crohn's Colitis 2019; 13 (09) 1158-1162
    CrossrefPubMedGoogle Scholar
  • 7 Quinn KP, Raffals LE. An update on the medical management of inflammatory pouch complications. Am J Gastroenterol 2020; 115 (09) 1439-1450
    CrossrefPubMedGoogle Scholar
  • 8 Dubinsky V, Reshef L, Bar N. et al. Predominantly antibiotic-resistant intestinal microbiome persists in patients with pouchitis who respond to antibiotic therapy. Gastroenterology 2020; 158 (03) 610-624.e13
    CrossrefPubMedGoogle Scholar
  • 9 Leach ST, Mitchell HM, Eng WR, Zhang L, Day AS. Sustained modulation of intestinal bacteria by exclusive enteral nutrition used to treat children with Crohn's disease. Aliment Pharmacol Ther 2008; 28 (06) 724-733
    CrossrefPubMedGoogle Scholar
  • 10 Grover Z, Muir R, Lewindon P. Exclusive enteral nutrition induces early clinical, mucosal and transmural remission in paediatric Crohn's disease. J Gastroenterol 2014; 49 (04) 638-645
    CrossrefPubMedGoogle Scholar
  • 11 Kaakoush NO, Day AS, Leach ST, Lemberg DA, Nielsen S, Mitchell HM. Effect of exclusive enteral nutrition on the microbiota of children with newly diagnosed Crohn's disease. Clin Transl Gastroenterol 2015; 6 (01) e71
    CrossrefPubMedGoogle Scholar
  • 12 Townsend CM, Parker CE, MacDonald JK. et al. Antibiotics for induction and maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2019; 2 (02) CD012730
    PubMedGoogle Scholar
  • 13 Glassner KL, Abraham BP, Quigley EMM. The microbiome and inflammatory bowel disease. J Allergy Clin Immunol 2020; 145 (01) 16-27
    CrossrefPubMedGoogle Scholar
  • 14 Gevers D, Kugathasan S, Denson LA. et al. The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe 2014; 15 (03) 382-392
    CrossrefPubMedGoogle Scholar
  • 15 Sartor RB, Wu GD. Roles for intestinal bacteria, viruses, and fungi in pathogenesis of inflammatory bowel diseases and therapeutic approaches. Gastroenterology 2017; 152 (02) 327-339.e4
    CrossrefPubMedGoogle Scholar
  • 16 Sokol H, Pigneur B, Watterlot L. et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A 2008; 105 (43) 16731-16736
    CrossrefPubMedGoogle Scholar
  • 17 Willing BP, Dicksved J, Halfvarson J. et al. A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology 2010; 139 (06) 1844-1854.e1
    CrossrefPubMedGoogle Scholar
  • 18 Joossens M, Huys G, Cnockaert M. et al. Dysbiosis of the faecal microbiota in patients with Crohn's disease and their unaffected relatives. Gut 2011; 60 (05) 631-637
    CrossrefPubMedGoogle Scholar
  • 19 Henke MT, Kenny DJ, Cassilly CD, Vlamakis H, Xavier RJ, Clardy J. Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn's disease, produces an inflammatory polysaccharide. Proc Natl Acad Sci U S A 2019; 116 (26) 12672-12677
    CrossrefPubMedGoogle Scholar
  • 20 Wlodarska M, Luo C, Kolde R. et al. Indoleacrylic acid produced by commensal peptostreptococcus species suppresses inflammation. Cell Host Microbe 2017; 22 (01) 25-37.e6
    CrossrefPubMedGoogle Scholar
  • 21 Duboc H, Rajca S, Rainteau D. et al. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut 2013; 62 (04) 531-539
    CrossrefPubMedGoogle Scholar
  • 22 Sinha SR, Haileselassie Y, Nguyen LP. et al. Dysbiosis-induced secondary bile acid deficiency promotes intestinal inflammation. Cell Host Microbe 2020; 27 (04) 659-670.e5
    CrossrefPubMedGoogle Scholar
  • 23 Darfeuille-Michaud A, Neut C, Barnich N. et al. Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease. Gastroenterology 1998; 115 (06) 1405-1413
    CrossrefPubMedGoogle Scholar
  • 24 Taurog JD, Richardson JA, Croft JT. et al. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med 1994; 180 (06) 2359-2364
    CrossrefPubMedGoogle Scholar
  • 25 Kullberg MC, Ward JM, Gorelick PL. et al. Helicobacter hepaticus triggers colitis in specific-pathogen-free interleukin-10 (IL-10)-deficient mice through an IL-12- and gamma interferon-dependent mechanism. Infect Immun 1998; 66 (11) 5157-5166
    CrossrefPubMedGoogle Scholar
  • 26 Mazmanian SK, Round JL, Kasper DL. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 2008; 453 (7195): 620-625
    CrossrefPubMedGoogle Scholar
  • 27 Garrett WS, Gallini CA, Yatsunenko T. et al. Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe 2010; 8 (03) 292-300
    CrossrefPubMedGoogle Scholar
  • 28 Norman JM, Handley SA, Baldridge MT. et al. Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 2015; 160 (03) 447-460
    CrossrefPubMedGoogle Scholar
  • 29 Chehoud C, Albenberg LG, Judge C. et al. Fungal signature in the gut microbiota of pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis 2015; 21 (08) 1948-1956
    CrossrefPubMedGoogle Scholar
  • 30 Sokol H, Leducq V, Aschard H. et al. Fungal microbiota dysbiosis in IBD. Gut 2017; 66 (06) 1039-1048
    CrossrefPubMedGoogle Scholar
  • 31 Shaw SY, Blanchard JF, Bernstein CN. Association between the use of antibiotics in the first year of life and pediatric inflammatory bowel disease. Am J Gastroenterol 2010; 105 (12) 2687-2692
    CrossrefPubMedGoogle Scholar
  • 32 Shaw SY, Blanchard JF, Bernstein CN. Association between the use of antibiotics and new diagnoses of Crohn's disease and ulcerative colitis. Am J Gastroenterol 2011; 106 (12) 2133-2142
    CrossrefPubMedGoogle Scholar
  • 33 Ungaro R, Bernstein CN, Gearry R. et al. Antibiotics associated with increased risk of new-onset Crohn's disease but not ulcerative colitis: a meta-analysis. Am J Gastroenterol 2014; 109 (11) 1728-1738
    CrossrefPubMedGoogle Scholar
  • 34 Becattini S, Taur Y, Pamer EG. Antibiotic-induced changes in the intestinal microbiota and disease. Trends Mol Med 2016; 22 (06) 458-478
    CrossrefPubMedGoogle Scholar
  • 35 Lange K, Buerger M, Stallmach A, Bruns T. Effects of antibiotics on gut microbiota. Dig Dis 2016; 34 (03) 260-268
    CrossrefPubMedGoogle Scholar
  • 36 Amre DK, D'Souza S, Morgan K. et al. Imbalances in dietary consumption of fatty acids, vegetables, and fruits are associated with risk for Crohn's disease in children. Am J Gastroenterol 2007; 102 (09) 2016-2025
    CrossrefPubMedGoogle Scholar
  • 37 Ananthakrishnan AN, Khalili H, Konijeti GG. et al. A prospective study of long-term intake of dietary fiber and risk of Crohn's disease and ulcerative colitis. Gastroenterology 2013; 145 (05) 970-977
    CrossrefPubMedGoogle Scholar
  • 38 Tanes C, Bittinger K, Gao Y. et al. Role of dietary fiber in the recovery of the human gut microbiome and its metabolome. Cell Host Microbe 2021; 29 (03) 394-407.e5
    CrossrefPubMedGoogle Scholar
  • 39 Smith PM, Howitt MR, Panikov N. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 2013; 341 (6145): 569-573
    CrossrefPubMedGoogle Scholar
  • 40 Liu JZ, van Sommeren S, Huang H. et al; International Multiple Sclerosis Genetics Consortium, International IBD Genetics Consortium. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet 2015; 47 (09) 979-986
    CrossrefPubMedGoogle Scholar
  • 41 Lavoie S, Conway KL, Lassen KG. et al. The Crohn's disease polymorphism, ATG16L1 T300A, alters the gut microbiota and enhances the local Th1/Th17 response. eLife 2019; 8: e39982
    CrossrefPubMedGoogle Scholar
  • 42 Lesage S, Zouali H, Cézard JP. et al; EPWG-IBD Group, EPIMAD Group, GETAID Group. CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease. Am J Hum Genet 2002; 70 (04) 845-857
    CrossrefPubMedGoogle Scholar
  • 43 Chu H, Khosravi A, Kusumawardhani IP. et al. Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease. Science 2016; 352 (6289): 1116-1120
    CrossrefPubMedGoogle Scholar
  • 44 Kolho K-L, Korpela K, Jaakkola T. et al. Fecal microbiota in pediatric inflammatory bowel disease and its relation to inflammation. Am J Gastroenterol 2015; 110 (06) 921-930
    CrossrefPubMedGoogle Scholar
  • 45 Höyhtyä M, Korpela K, Saqib S. et al. Quantitative fecal microbiota profiles relate to therapy response during induction with tumor necrosis factor α antagonist infliximab in pediatric inflammatory bowel disease. Inflamm Bowel Dis 2022; izac182 DOI: 10.1093/ibd/izac182.
    CrossrefPubMedGoogle Scholar
  • 46 Paramsothy S, Kamm MA, Kaakoush NO. et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet 2017; 389 (10075): 1218-1228
    CrossrefPubMedGoogle Scholar
  • 47 Rossen NG, Fuentes S, van der Spek MJ. et al. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology 2015; 149 (01) 110-118.e4
    CrossrefPubMedGoogle Scholar
  • 48 Kruis W, Fric P, Pokrotnieks J. et al. Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut 2004; 53 (11) 1617-1623
    CrossrefPubMedGoogle Scholar
  • 49 Rembacken BJ, Snelling AM, Hawkey PM, Chalmers DM, Axon AT. Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet 1999; 354 (9179): 635-639
    CrossrefPubMedGoogle Scholar
  • 50 Sood A, Midha V, Makharia GK. et al. The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin Gastroenterol Hepatol 2009; 7 (11) 1202-1209 , 1209.e1
    CrossrefPubMedGoogle Scholar
  • 51 Derwa Y, Gracie DJ, Hamlin PJ, Ford AC. Systematic review with meta-analysis: the efficacy of probiotics in inflammatory bowel disease. Aliment Pharmacol Ther 2017; 46 (04) 389-400
    CrossrefPubMedGoogle Scholar
  • 52 Federici S, Kredo-Russo S, Valdés-Mas R. et al. Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation. Cell 2022; 185 (16) 2879-2898.e24
    CrossrefPubMedGoogle Scholar
  • 53 Lewis JD, Sandler RS, Brotherton C. et al; DINE-CD Study Group. A randomized trial comparing the specific carbohydrate diet to a Mediterranean diet in adults with Crohn's disease. Gastroenterology 2021; 161 (03) 837-852.e9
    CrossrefPubMedGoogle Scholar