Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The gut microbiota in IBD

Abstract

IBD—ulcerative colitis and Crohn's disease—is emerging as a worldwide epidemic. An association between the increased incidence of IBD and environmental factors linked to socioeconomic development has been persistently detected in different parts of the world. The lifestyle in developed countries might impair the natural patterns of microbial colonization of the human gut. The interaction of microbes with mucosal immune compartments in the gut seems to have a major role in priming and regulating immunity. In IBD, mucosal lesions are generated by an excessive or dysregulated immune response against commensal microbes in the gut. In individuals with a genetic susceptibility to IBD, abnormal microbial colonization of the gastrointestinal tract might be the origin of such dysregulation. Developments in gene-sequencing technologies, as well as increased availability of powerful bioinformatic tools, have enabled novel insights into the microbial composition of the human gut microbiota and the effect of microbial communities on human physiology and disease. Studies that used these technologies indicate that dysbiosis (that is, abnormal microbiota composition) and decreased complexity of the gut microbial ecosystem are common features in patients with Crohn's disease or ulcerative colitis. Whether such changes are a cause or a consequence of the disease remains to be elucidated.

Key Points

  • Environmental factors are necessary contributors to the pathogenesis of IBD—most individuals with genetic susceptibility do not develop the disease—and are primarily responsible for its growing incidence around the globe

  • The lifestyle in developed countries can be linked with alterations in the microbial colonization of the human gut

  • Microbial colonization has an important effect on the instruction and regulation of the immune system

  • The gut microbiota is an essential factor in driving inflammation and the development of mucosal lesions in IBD; certain microbes exacerbate inflammation, but some others mitigate inflammation

  • Dysbiosis and decreased complexity of the gut microbial ecosystem are common features in patients with IBD

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Suggested model of perpetuation of intestinal inflammation in IBD.
Figure 2: Technologies to investigate the gut microbiota.
Figure 3: Dysbiosis in ulcerative colitis based on data by Lepage et al.57 from 62 participants.
Figure 4: Reduction of bacterial diversity in patients with Crohn's disease based on data by Manichanh et al.71 from 12 participants.

Similar content being viewed by others

References

  1. White, W. H. On simple ulcerative colitis and other rare intestinal ulcers. Guy's Hosp. Rep. 45, 131–162 (1888).

    Google Scholar 

  2. Crohn, B. B., Ginzburg, L. & Oppenheimer, G. D. Regional ileitis: a pathologic and clinical entity. JAMA 99, 1323–1329 (1932).

    Article  Google Scholar 

  3. Molodecky, N. A. et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142, 46–54 (2012).

    PubMed  Google Scholar 

  4. Lees, C. W., Barrett, J. C., Parkes, M. & Satsangi, J. New IBD genetics: common pathways with other diseases. Gut 60, 1739–1753 (2011).

    Article  CAS  Google Scholar 

  5. Hviid, A., Svanström, H. & Frisch, M. Antibiotic use and inflammatory bowel diseases in childhood. Gut 60, 49–54 (2011).

    Article  Google Scholar 

  6. Bager, P., Simonsen, J., Nielsen, N. M. & Frisch, M. Cesarean section and offspring's risk of inflammatory bowel disease: a national cohort study. Inflamm. Bowel Dis. 18, 857–862 (2012).

    Article  Google Scholar 

  7. Bernstein, C. N. & Shanahan, F. Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases. Gut 57, 1185–1191 (2008).

    Article  Google Scholar 

  8. De Filippo, C. et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl Acad. Sci. USA 107, 14691–14696 (2010).

    Article  Google Scholar 

  9. Guarner, F. et al. Mechanisms of disease: the hygiene hypothesis revisited. Nat. Clin. Pract. Gastroenterol. Hepatol. 3, 275–284 (2006).

    Article  CAS  Google Scholar 

  10. Asquith, M. & Powrie, F. An innately dangerous balancing act: intestinal homeostasis, inflammation, and colitis-associated cancer. J. Exp. Med. 207, 1573–1577 (2010).

    Article  CAS  Google Scholar 

  11. Brandtzaeg, P. Mucosal immunity: induction, dissemination, and effector functions. Scand. J. Immunol. 70, 505–515 (2009).

    Article  CAS  Google Scholar 

  12. Sartor, R. B. Microbial influences in inflammatory bowel diseases. Gastroenterology 134, 577–594 (2008).

    CAS  Google Scholar 

  13. Guarner, F. What is the role of the enteric commensal flora in IBD? Inflamm. Bowel Dis. 14 (Suppl. 2), S83–S84 (2008).

    Article  Google Scholar 

  14. D'Haens, G. R. et al. Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology 114, 262–267 (1998).

    Article  CAS  Google Scholar 

  15. Casellas, F. et al. Antiinflammatory effects of enterically coated amoxicillin-clavulanic acid in active ulcerative colitis. Inflamm. Bowel Dis. 4, 1–5 (1998).

    Article  CAS  Google Scholar 

  16. Macpherson, A., Khoo, U. Y., Forgacs, I., Philpott-Howard, J. & Bjarnason, I. Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria. Gut 38, 365–375 (1996).

    Article  CAS  Google Scholar 

  17. Pirzer, U., Schönhaar, A., Fleischer, B., Hermann, E. & Meyer zum Büschenfelde, K. H. Reactivity of infiltrating T lymphocytes with microbial antigens in Crohn's disease. Lancet 338, 1238–1239 (1991).

    Article  CAS  Google Scholar 

  18. Borruel, N. et al. Increased mucosal tumour necrosis factor α production in Crohn's disease can be downregulated ex vivo by probiotic bacteria. Gut 51, 659–664 (2002).

    Article  CAS  Google Scholar 

  19. Carol, M. et al. Modulation of apoptosis in intestinal lymphocytes by a probiotic bacteria in Crohn's disease. J. Leukoc. Biol. 79, 917–922 (2006).

    Article  CAS  Google Scholar 

  20. Llopis, M. et al. Lactobacillus casei downregulates commensals' inflammatory signals in Crohn's disease mucosa. Inflamm. Bowel Dis. 15, 275–283 (2009).

    Article  Google Scholar 

  21. Pender, S. L. Do metalloproteinases contribute to tissue destruction or remodeling in the inflamed gut? Inflamm. Bowel Dis. 14 (Suppl. 2), S136–S137 (2008).

    Article  Google Scholar 

  22. Borruel, N. et al. Effects of nonpathogenic bacteria on cytokine secretion by human intestinal mucosa. Am. J. Gastroenterol. 98, 865–870 (2003).

    Article  CAS  Google Scholar 

  23. Hart, A. L. et al. Modulation of human dendritic cell phenotype and function by probiotic bacteria. Gut 53, 1602–1609 (2004).

    Article  CAS  Google Scholar 

  24. Sokol, H. et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl Acad. Sci. USA 105, 16731–16736 (2008).

    Article  CAS  Google Scholar 

  25. Marwaha, A. K., Leung, N. J., McMurchy, A. N. & Levings, M. K. TH17 cells in autoimmunity and immunodeficiency: protective or pathogenic? Front. Immunol. 3, 129 (2012).

    Article  Google Scholar 

  26. Rook, G. A. Review series on helminths, immune modulation and the hygiene hypothesis: the broader implications of the hygiene hypothesis. Immunology 126, 3–11 (2009).

    Article  CAS  Google Scholar 

  27. Round, J. L. & Mazmanian, S. K. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9, 313–323 (2009).

    Article  CAS  Google Scholar 

  28. Kelly, D. et al. Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-γ and RelA. Nat. Immunol. 5, 104–112 (2004).

    Article  CAS  Google Scholar 

  29. Mazmanian, S. K., Round, J. L. & Kasper, D. L. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453, 620–625 (2008).

    Article  CAS  Google Scholar 

  30. Atarashi, K. et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337–341 (2011).

    Article  CAS  Google Scholar 

  31. Strober, W., Fuss, I. & Mannon, P. The fundamental basis of inflammatory bowel disease. J. Clin. Invest. 117, 514–521 (2007).

    Article  CAS  Google Scholar 

  32. Handelsman, J., Rondon, M. R., Brady, S. F., Clardy, J. & Goodman, R. M. Molecular biological access to the chemistry of unknown soil microbes: a new frontier for natural products. Chem. Biol. 5, R245–R249 (1998).

    Article  CAS  Google Scholar 

  33. Fox, G. E., Magrum, L. J., Balch, W. E., Wolfe, R. S. & Woese, C. R. Classification of methanogenic bacteria by 16S ribosomal RNA characterization. Proc. Natl Acad. Sci. USA 74, 4537–4541 (1977).

    Article  CAS  Google Scholar 

  34. Gill, S. R. et al. Metagenomic analysis of the human distal gut microbiome. Science 312, 1355–1359 (2006).

    Article  CAS  Google Scholar 

  35. Rodrigue, S. et al. Whole genome amplification and de novo assembly of single bacterial cells. PLoS ONE 4, e6864 (2009).

    Article  Google Scholar 

  36. The NIH Common Fund Office of Strategic Coordination. Human Microbiome Project [online], (2012).

  37. Nelson, K. E. et al. A catalog of reference genomes from the human microbiome. Science 328, 994–999 (2010).

    Article  CAS  Google Scholar 

  38. Proctor, L. M. The Human Microbiome Project in 2011 and beyond. Cell Host Microbe 10, 287–291 (2011).

    Article  CAS  Google Scholar 

  39. DeSantis, T. Z. et al. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl. Environ. Microbiol. 72, 5069–5072 (2006).

    Article  CAS  Google Scholar 

  40. Pruesse, E. et al. SILVA: a comprehensive online resource for quality checked and aligned ribosomal RNA sequence data compatible with ARB. Nucleic Acids Res. 35, 7188–7196 (2007).

    Article  CAS  Google Scholar 

  41. Cole, J. R. et al. The Ribosomal Database Project: improved alignments and new tools for rRNA analysis. Nucleic Acids Res. 37, D141–D145 (2009).

    Article  CAS  Google Scholar 

  42. Costello, E. K. et al. Bacterial community variation in human body habitats across space and time. Science 326, 1694–1697 (2009).

    Article  CAS  Google Scholar 

  43. Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65 (2010).

    Article  CAS  Google Scholar 

  44. MetaHIT. Metagenomics of the Human Gastrointestinal Tract [online], (2012).

  45. Gosalbes, M. J. et al. Metatranscriptomic approach to analyze the functional human gut microbiota. PLoS ONE 6, e17447 (2011).

    Article  CAS  Google Scholar 

  46. Frank, D. N. & Pace, N. R. Gastrointestinal microbiology enters the metagenomics era. Curr. Opin. Gastroenterol. 24, 4–10 (2008).

    Article  CAS  Google Scholar 

  47. Eckburg, P. B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).

    Article  Google Scholar 

  48. Caporaso, J. G. et al. Moving pictures of the human microbiome. Genome Biol. 12, R50 (2011).

    Article  Google Scholar 

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

    Article  Google Scholar 

  50. Arumugam, M. et al. Enterotypes of the human gut microbiome. Nature 473, 174–180 (2011).

    Article  CAS  Google Scholar 

  51. Wu, G. D. et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 334, 105–108 (2011).

    Article  CAS  Google Scholar 

  52. Ott, S. J. et al. Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut 53, 685–693 (2004).

    Article  CAS  Google Scholar 

  53. Mai, V., Braden, C. R., Heckendorf, J., Pironis, B. & Hirshon, J. M. Monitoring of stool microbiota in subjects with diarrhea indicates distortions in composition. J. Clin. Microbiol. 44, 4550–4552 (2006).

    Article  Google Scholar 

  54. Noor, S. O. et al. Ulcerative colitis and irritable bowel patients exhibit distinct abnormalities of the gut microbiota. BMC Gastroenterol. 12, 134 (2010).

    Article  Google Scholar 

  55. Frank, D. N. et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc. Natl Acad. Sci. USA 104, 13780–13785 (2007).

    Article  CAS  Google Scholar 

  56. Willing, B. P. et al. A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology 139, 1844–1854 (2010).

    Article  Google Scholar 

  57. Lepage, P. et al. Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis. Gastroenterology 141, 227–236 (2011).

    Article  Google Scholar 

  58. Martínez, C. et al. Unstable composition of the fecal microbiota in ulcerative colitis during clinical remission. Am. J. Gastroenterol. 103, 643–648 (2008).

    Article  Google Scholar 

  59. Rowan, F. et al. Desulfovibrio bacterial species are increased in ulcerative colitis. Dis. Colon Rectum 53, 1530–1536 (2010).

    Article  Google Scholar 

  60. Roediger, W. E., Moore, J. & Babidge, W. Colonic sulfide in pathogenesis and treatment of ulcerative colitis. Dig. Dis. Sci. 42, 1571–1579 (1997).

    Article  CAS  Google Scholar 

  61. Pitcher, M. C., Beatty, E. R. & Cummings, J. H. The contribution of sulphate reducing bacteria and 5-aminosalicylic acid to faecal sulphide in patients with ulcerative colitis. Gut 46, 64–72 (2000).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

  64. Ohkusa, T. et al. Induction of experimental ulcerative colitis by Fusobacterium varium isolated from colonic mucosa of patients with ulcerative colitis. Gut 52, 79–83 (2003).

    Article  CAS  Google Scholar 

  65. Strauss, J. et al. Invasive potential of gut mucosa-derived Fusobacterium nucleatum positively correlates with IBD status of the host. Inflamm. Bowel Dis. 17, 1971–1978 (2011).

    Article  Google Scholar 

  66. Sokol, H., Lepage, P., Seksik, P., Doré, J. & Marteau, P. Temperature gradient gel electrophoresis of fecal 16S rRNA reveals active Escherichia coli in the microbiota of patients with ulcerative colitis. J. Clin. Microbiol. 44, 3172–3177 (2006).

    Article  CAS  Google Scholar 

  67. Chassaing, B. & Darfeuille-Michaud, A. The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases. Gastroenterology 140, 1720–1728 (2011).

    Article  Google Scholar 

  68. Sokol, H. et al. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm. Bowel Dis. 15, 1183–1189 (2009).

    Article  CAS  Google Scholar 

  69. Varela, E. et al. Colonization by Faecalibacterium prausnitzii and maintenance of clinical remission in patients with ulcerative colitis. Gastroenterology 140, S-47 (2011).

    Article  Google Scholar 

  70. Selby, W. et al. Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn's disease. Gastroenterology 132, 2313–2319 (2007).

    Article  CAS  Google Scholar 

  71. Manichanh, C. et al. Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut 55, 205–211 (2006).

    Article  CAS  Google Scholar 

  72. Dicksved, J. et al. Molecular analysis of the gut microbiota of identical twins with Crohn's disease. ISME J. 2, 716–727 (2008).

    Article  CAS  Google Scholar 

  73. Kang, S. et al. Dysbiosis of fecal microbiota in Crohn's disease patients as revealed by a custom phylogenetic microarray. Inflamm. Bowel Dis. 16, 2034–2042 (2010).

    Article  Google Scholar 

  74. Scanlan, P. D., Shanahan, F., O'Mahony, C. & Marchesi, J. R. 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 (2006).

    Article  CAS  Google Scholar 

  75. Darfeuille-Michaud, A. et al. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology 127, 412–421 (2004).

    Article  Google Scholar 

  76. Martinez-Medina, M. et al. Molecular diversity of Escherichia coli in the human gut: new ecological evidence supporting the role of adherent-invasive E. coli (AIEC) in Crohn's disease. Inflamm. Bowel Dis. 15, 872–882 (2009).

    Article  Google Scholar 

  77. Chassaing, B. et al. Crohn disease-associated adherent-invasive E. coli bacteria target mouse and human Peyer's patches via long polar fimbriae. J. Clin. Invest. 121, 966–975 (2011).

    Article  CAS  Google Scholar 

  78. Shen, B. Acute and chronic pouchitis-pathogenesis, diagnosis and treatment. Nat. Rev. Gastroenterol. Hepatol. 9, 323–333 (2012).

    Article  CAS  Google Scholar 

  79. McLaughlin, S. D. et al. The bacteriology of pouchitis: a molecular phylogenetic analysis using 16S rRNA gene cloning and sequencing. Ann. Surg. 252, 90–98 (2010).

    Article  Google Scholar 

Download references

Acknowledgements

The authors received funding from the European Commission Seventh Framework Programme (MetaHIT, grant agreement HEALTH-F4-2007-201052), and Fondo de Investigaciones Sanitarias (FIS PI10/00902, Ministerio de Ciencia e Innovacion, Spain). CIBEREHD is funded by the Instituto de Salud Carlos III (Madrid, Spain).

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed equally to all aspects of this article.

Corresponding author

Correspondence to Francisco Guarner.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Manichanh, C., Borruel, N., Casellas, F. et al. The gut microbiota in IBD. Nat Rev Gastroenterol Hepatol 9, 599–608 (2012). https://doi.org/10.1038/nrgastro.2012.152

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2012.152

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing