Dietary Fiber Protects against Diabetic Nephropathy through Short-Chain Fatty Acid?Mediated Activation of G Protein?Coupled Receptors GPR43 and GPR109A

摘要

Significance Statement The gut microbiota and its metabolites, in particular short-chain fatty acids derived from gut microbes? fermentation of fiber, are emerging therapeutic targets for systemic inflammatory and metabolic diseases, including diabetic nephropathy. The authors report that high-fiber diets or supplementation with short-chain fatty acids (acetate, butyrate, or propionate) afforded protection against development of kidney disease in diabetic mice. Dietary fiber restored gut microbial ecology, corrected ?dysbiotic? changes, and increased production of short-chain fatty acids. Mice deficient in the metabolite-sensing G protein?coupled receptors GPR43 or GPR109A were not protected by short-chain fatty acids, suggesting that protection was mediated by downstream binding to these receptors. Tapping into the metabolic potential of the gut microbiota through diet may offer a novel approach to address diabetic nephropathy.