Gut microbiota-associated metabolites and microbial products in diabetic kidney disease: linking intestinal dysbiosis, inflammation, and renal fibrosis

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes and a leading cause of chronic kidney disease and end-stage kidney disease. Although hyperglycemia, oxidative stress, inflammation, podocyte injury, tubular damage, and renal fibrosis are central to DKD progression, these mechanisms do not fully explain the heterogeneity of renal outcomes among patients with diabetes. Human observational studies have linked intestinal dysbiosis and altered microbial metabolite profiles to DKD, while preclinical investigations have identified potential mechanisms connecting these changes with renal injury. In DKD, gut microbial dysbiosis is characterized by depletion of beneficial taxa such as Roseburia intestinalis and enrichment of potentially harmful bacteria such as Bacteroides stercoris and Ruminococcus gnavus , accompanied by reduced production of protective metabolites including short-chain fatty acids and indole-3-propionic acid. Conversely, potentially harmful molecules include microbiota-derived imidazole propionate, host–microbial co-metabolites such as trimethylamine N-oxide, indoxyl sulfate, and p-cresyl sulfate, and microbial products such as lipopolysaccharide, which may contribute to renal inflammatory and fibrotic responses through distinct mechanisms. This narrative review summarizes the roles of gut microbiota-associated metabolites and microbial products in DKD, emphasizing their biological origins, inflammatory and fibrotic mechanisms, evidence limitations, and translational potential. We also discuss the biomarker potential of microbial metabolites and therapeutic strategies targeting the gut–metabolite–kidney axis, including dietary fiber, prebiotics, postbiotics, pharmacological agents, natural compounds, and personalized microbiome-based interventions.