CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands
- PMID: 27158904
- PMCID: PMC5087285
- DOI: 10.1038/nm.4102
CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands
Abstract
Complex interactions between the host and the gut microbiota govern intestinal homeostasis but remain poorly understood. Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. CARD9 promotes recovery from colitis by promoting interleukin (IL)-22 production, and Card9(-/-) mice are more susceptible to colitis. The microbiota is altered in Card9(-/-) mice, and transfer of the microbiota from Card9(-/-) to wild-type, germ-free recipients increases their susceptibility to colitis. The microbiota from Card9(-/-) mice fails to metabolize tryptophan into metabolites that act as aryl hydrocarbon receptor (AHR) ligands. Intestinal inflammation is attenuated after inoculation of mice with three Lactobacillus strains capable of metabolizing tryptophan or by treatment with an AHR agonist. Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. Our findings reveal that host genes affect the composition and function of the gut microbiota, altering the production of microbial metabolites and intestinal inflammation.
Conflict of interest statement
The authors declare no competing financial interests.
Figures
Comment in
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IBD: Dysbiosis underlies CARD9 risk alleles in colitis.Nat Rev Gastroenterol Hepatol. 2016 Jun;13(6):316. doi: 10.1038/nrgastro.2016.82. Epub 2016 May 18. Nat Rev Gastroenterol Hepatol. 2016. PMID: 27188821 No abstract available.
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Mucosal immunology: Tryptophan triggers tranquillity.Nat Rev Immunol. 2016 May 27;16(6):338-9. doi: 10.1038/nri.2016.66. Nat Rev Immunol. 2016. PMID: 27231049 No abstract available.
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Regulating inflammation with microbial metabolites.Nat Med. 2016 Jun 7;22(6):581-3. doi: 10.1038/nm.4117. Nat Med. 2016. PMID: 27270775 No abstract available.
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References
-
- Molodecky NA, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142:46–54.e42. quiz e30. - PubMed
-
- Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol. 2015;12:205–217. - PubMed
-
- Hsu YMSM, et al. The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens. Nat Immunol. 2007;8:198–205. - PubMed
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