Top

Published in:

Open Access 01-01-2015 | Review

The gut microbiota and inflammatory bowel disease

Authors: Katsuyoshi Matsuoka, Takanori Kanai

Published in: Seminars in Immunopathology | Issue 1/2015

Abstract

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gut. Although the precise cause of IBD remains unknown, the most accepted hypothesis of IBD pathogenesis to date is that an aberrant immune response against the gut microbiota is triggered by environmental factors in a genetically susceptible host. The advancement of next-generation sequencing technology has enabled identification of various alterations of the gut microbiota composition in IBD. While some results related to dysbiosis in IBD are different between studies owing to variations of sample type, method of investigation, patient profiles, and medication, the most consistent observation in IBD is reduced bacterial diversity, a decrease of Firmicutes, and an increase of Proteobacteria. It has not yet been established how dysbiosis contributes to intestinal inflammation. Many of the known IBD susceptibility genes are associated with recognition and processing of bacteria, which is consistent with a role of the gut microbiota in the pathogenesis of IBD. A number of trials have shown that therapies correcting dysbiosis, including fecal microbiota transplantation and probiotics, are promising in IBD.

Rutgeerts P et al (1991) Effect of faecal stream diversion on recurrence of Crohn’s disease in the neoterminal ileum. Lancet 338:771–774PubMedCrossRef

Khan KJ et al (2011) Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis. Am J Gastroenterol 106:661–673. doi:10.1038/ajg.2011.72 PubMedCrossRef

Ananthakrishnan AN et al (2011) Strategies for the prevention of postoperative recurrence in Crohn’s disease: results of a decision analysis. Am J Gastroenterol 106:2009–2017. doi:10.1038/ajg.2011.237 PubMedCrossRef

Jostins L et al (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491:119–124. doi:10.1038/nature11582 PubMedCentralPubMedCrossRef

Eckburg PB et al (2005) Diversity of the human intestinal microbial flora. Science 308:1635–1638. doi:10.1126/science.1110591 PubMedCentralPubMedCrossRef

Frank DN et al (2007) Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A 104:13780–13785. doi:10.1073/pnas.0706625104 PubMedCentralPubMedCrossRef

Manichanh C et al (2006) Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 55:205–211. doi:10.1136/gut.2005.073817 PubMedCentralPubMedCrossRef

Willing BP et al (2010) A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology 139(1844–1854):e1841. doi:10.1053/j.gastro.2010.08.049

Tong M et al (2013) A modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel disease. PLoS One 8:e80702. doi:10.1371/journal.pone.0080702 PubMedCentralPubMedCrossRef

10.

Gophna U et al (2006) Differences between tissue-associated intestinal microfloras of patients with Crohn’s disease and ulcerative colitis. J Clin Microbiol 44:4136–4141. doi:10.1128/jcm.01004-06 PubMedCentralPubMedCrossRef

11.

Scanlan PD et al (2006) Culture-independent analyses of temporal variation of the dominant fecal microbiota and targeted bacterial subgroups in Crohn’s disease. J Clin Microbiol 44:3980–3988. doi:10.1128/jcm.00312-06 PubMedCentralPubMedCrossRef

12.

Peterson DA et al (2008) Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases. Cell Host Microbe 3:417–427. doi:10.1016/j.chom.2008.05.001 PubMedCentralPubMedCrossRef

13.

Sokol H et al (2008) Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A 105:16731–16736. doi:10.1073/pnas.0804812105 PubMedCentralPubMedCrossRef

14.

Wang W et al (2014) Increased proportions of Bifidobacterium and the Lactobacillus group and loss of butyrate-producing bacteria in inflammatory bowel disease. J Clin Microbiol 52:398–406. doi:10.1128/jcm.01500-13 PubMedCentralPubMedCrossRef

15.

Andoh A et al (2011) Comparison of the fecal microbiota profiles between ulcerative colitis and Crohn’s disease using terminal restriction fragment length polymorphism analysis. J Gastroenterol 46:479–486. doi:10.1007/s00535-010-0368-4 PubMedCrossRef

16.

Takaishi H et al (2008) Imbalance in intestinal microflora constitution could be involved in the pathogenesis of inflammatory bowel disease. Int J Med Microbiol 298:463–472. doi:10.1016/j.ijmm.2007.07.016 PubMedCrossRef

17.

Martinez C et al (2008) Unstable composition of the fecal microbiota in ulcerative colitis during clinical remission. Am J Gastroenterol 103:643–648. doi:10.1111/j.1572-0241.2007.01592.x PubMedCrossRef

18.

Ott SJ et al (2008) Dynamics of the mucosa-associated flora in ulcerative colitis patients during remission and clinical relapse. J Clin Microbiol 46:3510–3513. doi:10.1128/jcm.01512-08 PubMedCentralPubMedCrossRef

19.

Andrews CN et al (2011) Mesalazine (5-aminosalicylic acid) alters faecal bacterial profiles, but not mucosal proteolytic activity in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 34:374–383. doi:10.1111/j.1365-2036.2011.04732.x PubMedCrossRef

20.

Gevers D et al (2014) The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 15:382–392. doi:10.1016/j.chom.2014.02.005 PubMedCrossRef

21.

Lepage P et al (2005) Biodiversity of the mucosa-associated microbiota is stable along the distal digestive tract in healthy individuals and patients with IBD. Inflamm Bowel Dis 11:473–480PubMedCrossRef

22.

Swidsinski A et al (2002) Mucosal flora in inflammatory bowel disease. Gastroenterology 122:44–54PubMedCrossRef

23.

Schultsz C et al (1999) The intestinal mucus layer from patients with inflammatory bowel disease harbors high numbers of bacteria compared with controls. Gastroenterology 117:1089–1097PubMedCrossRef

24.

Walker AW et al (2011) High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease. BMC Microbiol 11:7. doi:10.1186/1471-2180-11-7 PubMedCentralPubMedCrossRef

25.

Lepage P et al (2011) Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis. Gastroenterology 141:227–236. doi:10.1053/j.gastro.2011.04.011 PubMedCrossRef

26.

Varela E et al (2013) Colonisation by Faecalibacterium prausnitzii and maintenance of clinical remission in patients with ulcerative colitis. Aliment Pharmacol Ther 38:151–161. doi:10.1111/apt.12365 PubMedCrossRef

27.

Joossens M et al (2011) Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives. Gut 60:631–637. doi:10.1136/gut.2010.223263 PubMedCrossRef

28.

Frank DN et al (2011) Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. Inflamm Bowel Dis 17:179–184. doi:10.1002/ibd.21339 PubMedCrossRef

29.

Dey N et al (2013) Association of gut microbiota with post-operative clinical course in Crohn’s disease. BMC Gastroenterol 13:131. doi:10.1186/1471-230x-13-131 PubMedCentralPubMedCrossRef

30.

Feller M et al (2007) Mycobacterium avium subspecies paratuberculosis and Crohn’s disease: a systematic review and meta-analysis. Lancet Infect Dis 7:607–613. doi:10.1016/s1473-3099(07)70211-6 PubMedCrossRef

31.

Selby W et al (2007) Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn’s disease. Gastroenterology 132:2313–2319. doi:10.1053/j.gastro.2007.03.031 PubMedCrossRef

32.

Barnich N, Darfeuille-Michaud A (2007) Adherent-invasive Escherichia coli and Crohn’s disease. Curr Opin Gastroenterol 23:16–20. doi:10.1097/MOG.0b013e3280105a38 PubMedCrossRef

33.

Ohkusa T et al (1993) Bacterial invasion into the colonic mucosa in ulcerative colitis. J Gastroenterol Hepatol 8:116–118PubMedCrossRef

34.

Ohkusa T et al (2002) Fusobacterium varium localized in the colonic mucosa of patients with ulcerative colitis stimulates species-specific antibody. J Gastroenterol Hepatol 17:849–853PubMedCrossRef

35.

Ohkusa T, Okayasu I, Ogihara T, Morita K, Ogawa M, Sato N (2003) Induction of experimental ulcerative colitis by Fusobacterium varium isolated from colonic mucosa of patients with ulcerative colitis. Gut 52(1):79–83PubMedCentralPubMedCrossRef

36.

Ohkusa T et al (2005) Effectiveness of antibiotic combination therapy in patients with active ulcerative colitis: a randomized, controlled pilot trial with long-term follow-up. Scand J Gastroenterol 40:1334–1342. doi:10.1080/00365520510023648 PubMedCrossRef

37.

Lees CW et al (2011) New IBD genetics: common pathways with other diseases. Gut 60:1739–1753. doi:10.1136/gut.2009.199679 PubMedCrossRef

38.

Wehkamp J et al (2004) NOD2 (CARD15) mutations in Crohn’s disease are associated with diminished mucosal alpha-defensin expression. Gut 53:1658–1664. doi:10.1136/gut.2003.032805 PubMedCentralPubMedCrossRef

39.

Noguchi E et al (2009) A Crohn’s disease-associated NOD2 mutation suppresses transcription of human IL10 by inhibiting activity of the nuclear ribonucleoprotein hnRNP-A1. Nat Immunol 10:471–479. doi:10.1038/ni.1722 PubMedCentralPubMedCrossRef

40.

Cooney R et al (2010) NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med 16:90–97. doi:10.1038/nm.2069 PubMedCrossRef

41.

Salzman NH et al (2010) Enteric defensins are essential regulators of intestinal microbial ecology. Nat Immunol 11:76–83. doi:10.1038/ni.1825 PubMedCentralPubMedCrossRef

42.

VanDussen KL et al (2014) Genetic variants synthesize to produce paneth cell phenotypes that define subtypes of Crohn’s disease. Gastroenterology 146:200–209. doi:10.1053/j.gastro.2013.09.048 PubMedCrossRef

43.

Cadwell K et al (2010) Virus-plus-susceptibility gene interaction determines Crohn’s disease gene Atg16L1 phenotypes in intestine. Cell 141:1135–1145. doi:10.1016/j.cell.2010.05.009 PubMedCentralPubMedCrossRef

44.

Adolph TE et al (2013) Paneth cells as a site of origin for intestinal inflammation. Nature 503:272–276. doi:10.1038/nature12599 PubMed

45.

Kim SC et al (2005) Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria. Gastroenterology 128:891–906PubMedCrossRef

46.

Garrett WS et al (2007) Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 131:33–45. doi:10.1016/j.cell.2007.08.017 PubMedCentralPubMedCrossRef

47.

Qin J et al (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59–65. doi:10.1038/nature08821 PubMedCentralPubMedCrossRef

48.

Gill SR et al (2006) Metagenomic analysis of the human distal gut microbiome. Science 312:1355–1359. doi:10.1126/science.1124234 PubMedCentralPubMedCrossRef

49.

Morgan XC et al (2012) Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol 13:R79. doi:10.1186/gb-2012-13-9-r79 PubMedCentralPubMedCrossRef

50.

Furusawa Y et al (2013) Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504:446–450. doi:10.1038/nature12721 PubMedCrossRef

51.

Pitcher MC et al (2000) The contribution of sulphate reducing bacteria and 5-aminosalicylic acid to faecal sulphide in patients with ulcerative colitis. Gut 46:64–72PubMedCentralPubMedCrossRef

52.

Ivanov II et al (2009) Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139:485–498. doi:10.1016/j.cell.2009.09.033 PubMedCentralPubMedCrossRef

53.

Caselli M et al (2013) Segmented filamentous bacteria-like organisms in histological slides of ileo-cecal valves in patients with ulcerative colitis. Am J Gastroenterol 108:860–861. doi:10.1038/ajg.2013.61 PubMedCrossRef

54.

van Nood E et al (2013) Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 368:407–415. doi:10.1056/NEJMoa1205037 PubMedCrossRef

55.

Bennet JD, Brinkman M (1989) Treatment of ulcerative colitis by implantation of normal colonic flora. Lancet 1:164PubMedCrossRef

56.

Anderson JL et al (2012) Systematic review: faecal microbiota transplantation in the management of inflammatory bowel disease. Aliment Pharmacol Ther 36:503–516. doi:10.1111/j.1365-2036.2012.05220.x PubMedCrossRef

57.

Angelberger S et al (2013) Temporal bacterial community dynamics vary among ulcerative colitis patients after fecal microbiota transplantation. Am J Gastroenterol 108:1620–1630. doi:10.1038/ajg.2013.257 PubMedCrossRef

58.

Kump PK et al (2013) Alteration of intestinal dysbiosis by fecal microbiota transplantation does not induce remission in patients with chronic active ulcerative colitis. Inflamm Bowel Dis 19:2155–2165. doi:10.1097/MIB.0b013e31829ea325 PubMedCrossRef

59.

Kunde S et al (2013) Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis. J Pediatr Gastroenterol Nutr 56:597–601. doi:10.1097/MPG.0b013e318292fa0d PubMedCrossRef

60.

Gionchetti P et al (2000) Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 119:305–309PubMedCrossRef

61.

Mimura T et al (2004) Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut 53:108–114PubMedCentralPubMedCrossRef

62.

Tursi A et al (2010) Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study. Am J Gastroenterol 105:2218–2227. doi:10.1038/ajg.2010.218 PubMedCentralPubMedCrossRef

63.

Sood A et al (2009) The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin Gastroenterol Hepatol 7:1202–1209. doi:10.1016/j.cgh.2009.07.016, 1209 e1201PubMedCrossRef

64.

Miele E et al (2009) Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis. Am J Gastroenterol 104:437–443. doi:10.1038/ajg.2008.118 PubMedCrossRef

65.

Soo I et al (2008) VSL#3 probiotic upregulates intestinal mucosal alkaline sphingomyelinase and reduces inflammation. Can J Gastroenterol 22:237–242PubMedCentralPubMed

66.

Rembacken BJ et al (1999) Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet 354:635–639PubMedCrossRef

67.

Kruis W et al (2004) Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut 53:1617–1623. doi:10.1136/gut.2003.037747 PubMedCentralPubMedCrossRef

68.

Kruis W et al (1997) Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther 11:853–858PubMedCrossRef

69.

Kamada N et al (2008) Nonpathogenic Escherichia coli strain Nissle 1917 inhibits signal transduction in intestinal epithelial cells. Infect Immun 76:214–220. doi:10.1128/iai.01193-07 PubMedCentralPubMedCrossRef

70.

Zocco MA et al (2006) Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther 23:1567–1574. doi:10.1111/j.1365-2036.2006.02927.x PubMedCrossRef

71.

Bousvaros A et al (2005) A randomized, double-blind trial of Lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn’s disease. Inflamm Bowel Dis 11:833–839PubMedCrossRef

72.

Schultz M et al (2004) Lactobacillus GG in inducing and maintaining remission of Crohn’s disease. BMC Gastroenterol 4:5. doi:10.1186/1471-230x-4-5 PubMedCentralPubMedCrossRef

73.

Furrie E et al (2005) Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut 54:242–249. doi:10.1136/gut.2004.044834 PubMedCentralPubMedCrossRef

74.

Kato K et al (2004) Randomized placebo-controlled trial assessing the effect of bifidobacteria-fermented milk on active ulcerative colitis. Aliment Pharmacol Ther 20:1133–1141. doi:10.1111/j.1365-2036.2004.02268.x PubMedCrossRef

75.

Ishikawa H et al (2003) Randomized controlled trial of the effect of bifidobacteria-fermented milk on ulcerative colitis. J Am Coll Nutr 22:56–63PubMedCrossRef

76.

Hayashi A et al (2013) A single strain of Clostridium butyricum induces intestinal IL-10-producing macrophages to suppress acute experimental colitis in mice. Cell Host Microbe 13:711–722. doi:10.1016/j.chom.2013.05.013 PubMedCrossRef

Title: The gut microbiota and inflammatory bowel disease
Authors: Katsuyoshi Matsuoka
Takanori Kanai
Publication date: 01-01-2015
Publisher: Springer Berlin Heidelberg
Published in: Seminars in Immunopathology / Issue 1/2015
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-014-0454-4

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2015

Impact of commensal microbiota on the host pathophysiology: focusing on immunity and inflammation

Microbiome and cancer

Toward the comprehensive understanding of the gut ecosystem via metabolomics-based integrated omics approach

Innate lymphoid cells, possible interaction with microbiota

Inflammasomes and the microbiota—partners in the preservation of mucosal homeostasis

Microbiome/microbiota and allergies

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage