Gut microbiota and diabetic kidney diseases: Pathogenesis and therapeutic perspectives

Figure 1 Pathogenic associations between gut dysbiotic microbiota and development of diabetic kidney diseases from the gut-kidney axis. On the one hand, endotoxins and uremic toxins accumulate because of gut microbiota dysbiosis and leak into the systemic circulation via a damaged gut barrier, which effectuates inflammation and nephrotoxicity. On the other hand, the dysbiotic microbiota results in a decrease of short chain fatty acids (SCFAs)-producing gut microbiota. SCFAs can activate transmembrane G protein-coupled receptors, which further stimulate secretion of glucagon-like peptide-1. In summary, SCFAs production in normal condition stabilizes the blood sugar level and presents protective effects on kidney cells. LPS: Lipopolysaccharides; SCFA: Short chain fatty acids; GPR: G protein-coupled receptors; GLP-1: Glucagon-like peptide-1; NF-κB: Nuclear factor kappa beta; TLR4: Toll-like receptor 4; GBM: Glomerular basement membrane; A: Means inhibition; →: Means activation.