Research progress on the role of gut microbiota dysregulation in the pathogenesis of diabetic nephropathy

There are about over 100 trillion microbial cells in human gut,which affect the nutritional,metabolic,physiological and immune functions of the host.This paper reviews the differences in gut microbiota between patients with diabetic nephropathy(DN)and healthy people.These differences lead to the disorder of symbiotic relationship,which may have induced the progression of DN,as well as targeted interventions to reconstruct the symbiotic relationship.Recent studies have found that endotoxin from intestinal bacteria and a large number of toxic metabolites were produced by fermentation of gut microbiota,such as trimethylamine-N-oxide,indoxyl sulfate and p-cresol sulfate,leading to the disruption of intestinal barrier function.Endotoxin and bacterial metabolites,entering the systemic circulation,were involved in DN progression by mediating inflammatory responses,renin-angiotensin-system and vascular injury.The reduction of some beneficial bacterial metabolites in DN patients,such as short-chain fatty acids,would weak body energy metabolism and destroy glucose homeostasis.In addition,gut microbiota is essential for the conversion of bile acids,and plays an important role in the development of DN by synthesizing secondary bile acids and regulating glucose and metabolic balance through foresaid X receptor(FXR)and G protein-coupled bile acid receptor(TGR5).Animal and clinical studies have revealed that probiotics,prebiotics,fecal microbiota transplantation,and Chinese medicine intervention may have potential therapeutic effects in maintaining a metabolically balanced gut microbiota to reduce the progression of DN,end-stage renal disease and cardiovascular complications.