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The role of bacteria and pattern-recognition receptors in Crohn's disease

A Correction to this article was published on 04 May 2011

This article has been updated

Abstract

Crohn's disease is widely regarded as a multifactorial disease, and evidence from human and animal studies suggests that bacteria have an instrumental role in its pathogenesis. Comparison of the intestinal microbiota of patients with Crohn's disease to that of healthy controls has revealed compositional changes. In most studies these changes are characterized by an increase in the abundance of Bacteroidetes and Proteobacteria and a decrease in that of Firmicutes. In addition, a number of specific mucosa-associated bacteria have been postulated to have a role in Crohn's disease, including Mycobacterium avium subspecies paratuberculosis, adherent and invasive Escherichia coli, Campylobacter and Helicobacter species. The association between mutations in pattern-recognition receptors (Toll-like receptors and Nod-like receptors) and autophagy proteins and Crohn's disease provides further evidence to suggest that defective sensing and killing of bacteria may drive the onset of disease. In this Review, we present recent advances in understanding the role of bacteria and the contribution of pattern-recognition receptors and autophagy in the pathogenesis of Crohn's disease.

Key Points

  • Current evidence suggests that the diversity and abundance of specific groups of bacteria differs between patients with Crohn's disease and healthy controls

  • To date, no specific groups or any single bacterium has been definitively associated with the etiology of Crohn's disease

  • Polymorphisms in pattern-recognition receptors and autophagy proteins are associated with susceptibility to Crohn's disease

  • Defective sensing and killing of bacteria owing to impaired pattern-recognition receptors, autophagy and defensin production may have a role in the etiopathogenesis of Crohn's disease

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Figure 1: Possible pathways in the development of Crohn's disease.
Figure 2: Bacterial recognition and signaling via pattern-recognition receptors and autophagy in Crohn's disease.

Change history

  • 18 March 2011

    In the Review by Man et al. published in the March 2011 issue of Nature Reviews Gastroenterology & Hepatology, MyD88 was incorrectly labeled as TRIF and shown in yellow instead of purple in Figure 2. The error has been corrected for the HTML and PDF versions of the article.

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Acknowledgements

We apologize to our colleagues whose work was not cited due to space limitations. We thank the National Health and Medical Research Council (NHMRC) of Australia and the Broad Medical Foundation for funding our research studies in Crohn's disease. We would also like to acknowledge Dr. P. Tourlomousis and Dr. C. Bryant (University of Cambridge) for providing thoughtful feedback on the manuscript. S. M. M. is a recipient of a Cambridge International Scholarship, and N. O. K. is a recipient of a NHMRC Postdoctoral Training Fellowship.

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Man, S., Kaakoush, N. & Mitchell, H. The role of bacteria and pattern-recognition receptors in Crohn's disease. Nat Rev Gastroenterol Hepatol 8, 152–168 (2011). https://doi.org/10.1038/nrgastro.2011.3

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