Li YJ, Chen X, Kwan TK, et al. - In order to explore the impact of dietary fiber on the development of experimental diabetic nephropathy, the authors used streptozotocin to induce diabetes in wild-type C57BL/6 and knockout mice lacking the genes encoding G protein–coupled receptors GPR43 or GPR109A. In drinking water, diabetic mice were randomized to high-fiber, normal chow, or zero-fiber diets, or short-chain fatty acids (SCFAs). According to results, diabetic mice fed a high-fiber diet were significantly less likely to experience diabetic nephropathy, showing fewer albuminuria, glomerular hypertrophy, podocyte injury, and interstitial fibrosis relative to diabetic controls fed normal chow or a zero-fiber diet. Dietary fiber protects against diabetic nephropathy by modulating the gut microbiota, enriching the bacteria that create SCFA, and increasing the production of SCFA. GPR43 and GPR109A are crucial to protecting against this condition mediated by SCFA. Interventions targeting the gut microbiota require more work in diabetic nephropathy as a novel renoprotective therapy.