Inappropriate diet and hygiene status affect the progression of diabetic kidney disease by causing dysbiosis.

Objective: Although the effects of an unhealthy diet on the risks of diabetes and its renal complications are well understood, the effects of hygiene status have not been fully elucidated.

Research methods and procedures: We created four groups of mice according to the diet fed (standard [SD] or high-fat [HFD]) and their living environment (conventional [CV] or specific pathogen-free [SPF]), and characterized the extent of their kidney pathology, their gut microbiota, and their fecal short-chain fatty acid (SCFA) concentrations.

Results: The body masses and glycated hemoglobin levels of the HFD and CV groups were significantly higher than those of the SD and SPF groups, respectively. The renal mRNA expression of markers of inflammation and fibrosis and the protein level of CD31 were higher in the HFD and CV groups than in the SD and SPF groups, respectively. Although the alpha diversities and total SCFA concentrations of the HFD and CV groups were significantly lower than those of the SD and SPF groups, respectively, the mRNA expression of genes involved in inflammation, innate immunity, tight junctions, and glucose transporters in the gut was only affected by HFD.

Conclusions: Gut microbial dysbiosis, owing to the combined effects of inappropriate diet and excessive hygiene, accompanied by lower intestinal SCFA production, may contribute to the development and/or progression of diabetes and diabetic kidney disease through the induction of inflammation and fibrosis.