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Novel players in coeliac disease pathogenesis: role of the gut microbiota

Key Points

  • The intestinal microbiota coexists with its host in a continuum between homeostasis and pathogenicity; the upper gastrointestinal tract harbours a gut microbiota that is affected compositionally and metabolically by food components

  • Coeliac disease is a chronic immune-mediated enteropathy caused by dietary gluten in genetically susceptible individuals

  • The role of microbial factors in coeliac disease pathogenesis has been suggested

  • Although clinical studies demonstrate that microbial changes are associated with coeliac disease, the individual microbes involved and underlying mechanisms remain elusive

  • Emerging data in gnotobiotic models indicate that the intestinal microbiota has a complex modulatory role in host immune responses to gluten

  • A deeper understanding of the precise role of microbes in coeliac disease pathogenesis will aid in the development of microbiota-modulating strategies, such as probiotics, to prevent or help treat the disease

Abstract

Several studies point towards alteration in gut microbiota composition and function in coeliac disease, some of which can precede the onset of disease and/or persist when patients are on a gluten-free diet. Evidence also exists that the gut microbiota might promote or reduce coeliac-disease-associated immunopathology. However, additional studies are required in humans and in mice (using gnotobiotic technology) to determine cause–effect relationships and to identify agents for modulating the gut microbiota as a therapeutic or preventative approach for coeliac disease. In this Review, we summarize the current evidence for altered gut microbiota composition in coeliac disease and discuss how the interplay between host genetics, environmental factors and the intestinal microbiota might contribute to its pathogenesis. Moreover, we highlight the importance of utilizing animal models and long-term clinical studies to gain insight into the mechanisms through which host–microbial interactions can influence host responses to gluten.

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Figure 1: Development of the gut microbiota.
Figure 2: Gut microbiota shapes host immunity.
Figure 3: Potential microbial modulation of coeliac disease pathogenesis.
Figure 4: Modulation of host responses to gluten by the composition of the gut microbiota.

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Acknowledgements

The authors are supported by grants from the Canadian Institutes of Health Research to E.F.V. (MOP 123282); and the Digestive Diseases Research Core Centre (DK42086) at the University of Chicago and from the NIH (RO1DK67180) to B.J. E.F.V. holds a Canada Research Chair and H.J.G. a Canadian Celiac Association fellowship.

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Summary of microbial alterations in patients with coeliac disease (DOC 117 kb)

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Verdu, E., Galipeau, H. & Jabri, B. Novel players in coeliac disease pathogenesis: role of the gut microbiota. Nat Rev Gastroenterol Hepatol 12, 497–506 (2015). https://doi.org/10.1038/nrgastro.2015.90

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