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.
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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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.
The authors declare no competing financial interests.
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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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