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IBD—what role do Proteobacteria play?

Abstract

The gastrointestinal microbiota has come to the fore in the search for the causes of IBD. This shift has largely been driven by the finding of genetic polymorphisms involved in gastrointestinal innate immunity (particularly polymorphisms in NOD2 and genes involved in autophagy) and alterations in the composition of the microbiota that might result in inflammation (so-called dysbiosis). Microbial diversity studies have continually demonstrated an expansion of the Proteobacteria phylum in patients with IBD. Individual Proteobacteria, in particular (adherent-invasive) Escherichia coli, Campylobacter concisus and enterohepatic Helicobacter, have all been associated with the pathogenesis of IBD. In this Review, we comprehensively describe the various associations of Proteobacteria and IBD. We also examine the importance of pattern recognition in the extracellular innate immune response of the host with particular reference to Proteobacteria, and postulate that Proteobacteria with adherent and invasive properties might exploit host defenses, drive proinflammatory change, alter the intestinal microbiota in favor of dysbiosis and ultimately lead to the development of IBD.

Key Points

  • The current paradigm of the pathogenesis of IBD involves a genetically and/or immunologically predisposed host responding inappropriately to an altered gastrointestinal microbiota, which leads to a protracted immune response and chronic inflammation

  • Proteobacteria are intricately involved in these luminal dysbiotic changes, wherein there is a breakdown in the balance of putative pathogenic bacteria and protective commensal bacteria

  • A subset of Proteobacteria with adherent-invasive capabilities potentially exploit the genetic defects of pathogen recognition and bacterial clearance, allowing them to perpetuate unchecked and providing the trigger that drives inflammation

  • The known genetic defects of pattern recognition receptors associated with susceptibility in developing IBD may paradoxically tilt the balance of the luminal microbiota towards pathogenic Gram-negative bacteria, in particular members of the Proteobacteria phylum

  • Studies correlating the genetic makeup of the host and the composition of the luminal microbiota will elucidate the relationship of Proteobacteria and the host immune system and the extent of its disruption in IBD

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Figure 1
Figure 2: The role of Proteobacteria in the postulated pathogenesis of IBD.

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Acknowledgements

Funding to Dr Hansen was provided by a Clinical Academic Training Fellowship from the Chief Scientist Office in Scotland (CAF/08/01). Other sources of funding for IBD research within the group include The Broad Medical Research Program, Crohn's in Childhood Research Association, NHS Grampian Hospital Endowments and Gastrointestinal Unit Hospital Research Funds.

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I. Mukhopadhya, R. Hansen and G. L. Hold all contributed to all aspects of this manuscript. E. M. El-Omar contributed to the discussion of content and review of the manuscript.

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Correspondence to Georgina L. Hold.

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Mukhopadhya, I., Hansen, R., El-Omar, E. et al. IBD—what role do Proteobacteria play?. Nat Rev Gastroenterol Hepatol 9, 219–230 (2012). https://doi.org/10.1038/nrgastro.2012.14

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