Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome

Laurence Macia, Jian Tan, Angelica T Vieira, Katie Leach, Dragana Stanley, Suzanne Luong, Mikako Maruya, Craig McKenzie, Atsushi Hijikata, Connie H Y Wong, Lauren Clare Binge, Alison N Thorburn, Nina Chevalier, Caroline Ang Kim Lian, Eliana Marino Moreno, Remy Robert, Stefan Offermanns, Mauro M Teixeira, Robert J Moore, Richard A FlavellSidonia Fagarasan, Charles R Mackay

Research output: Contribution to journalArticleResearchpeer-review

416 Citations (Scopus)

Abstract

Diet and the gut microbiota may underpin numerous human diseases. A major metabolic product of commensal bacteria are short-chain fatty acids (SCFAs) that derive from fermentation of dietary fibre. Here we show that diets deficient or low in fibre exacerbate colitis development, while very high intake of dietary fibre or the SCFA acetate protects against colitis. SCFAs binding to the metabolite-sensing receptors GPR43 and GPR109A in non-haematopoietic cells mediate these protective effects. The inflammasome pathway has hitherto been reported as a principal pathway promoting gut epithelial integrity. SCFAs binding to GPR43 on colonic epithelial cells stimulates K(+) efflux and hyperpolarization, which lead to NLRP3 inflammasome activation. Dietary fibre also shapes gut bacterial ecology, resulting in bacterial species that are more effective for inflammasome activation. SCFAs and metabolite receptors thus explain health benefits of dietary fibre, and how metabolite signals feed through to a major pathway for gut homeostasis.
Original languageEnglish
Pages (from-to)1 - 15
Number of pages15
JournalNature Communications
Volume6
Issue number(Art. No: 7734)
DOIs
Publication statusPublished - 2015

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