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

Citations Over TimeTop 1% of 2015 papers

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.

Related Papers

• → Metagenomic and metabolomic analyses unveil dysbiosis of gut microbiota in chronic heart failure patients(2018)359 cited
• → Indole-3-carbinol prevents colitis and associated microbial dysbiosis in an IL-22–dependent manner(2020)141 cited
• → Quercetin improves gut dysbiosis in antibiotic-treated mice(2020)121 cited
• → Traumatic Brain Injury Induces Gastrointestinal Dysfunction and Dysbiosis of Gut Microbiota Accompanied by Alterations of Bile Acid Profile(2021)86 cited
• → Gut Microbiota and Derived Short-Chain Fatty Acids Are Linked to Evolution of Heart Failure Patients(2023)36 cited