Vitamin D is involved in the effects of the intestinal flora and its related metabolite TMAO on perirenal fat and kidneys in mice with DKD

Abstract Vitamin D directly exerts a protective effect on the kidneys of individuals with diabetic kidney disease (DKD) in our previous study. However, whether it has an effect on perirenal adipose tissue (PRAT) or the intestinal flora and its metabolites (trimethylamine N-oxide, TMAO) is unclear. We found that 1,25-(OH) 2 D 3 could improve the dysbiosis of the intestinal flora of mice with DKD, increase the abundance of beneficial bacteria such as lactic acid bacteria, decrease the abundance of harmful bacteria such as Escherichia , reduce the pathological changes in kidney histopathology, reduce fat infiltration, and downregulate the mRNA expression of TLR4 and NF-κB in kidney tissue. We also found that the serum TMAO concentration in mice with DKD was significantly higher than that of the control group, and serum TMAO content was significantly positively correlated with urine ACR. In addition, vitamin D stimulated the expression of the surface markers PGC1α, UCP-1 and VDR in the PRAT in mice with DKD, and TMAO downregulated the expression of PRAT and renal VDR. The above results show that the renal protective effect of 1,25-(OH) 2 D 3 on mice with DKD may also be related to the improvement of the intestinal mucosal barrier, composition of the intestinal flora and its metabolites, inhibition of the TLR4/NF-κB inflammatory pathway and reduction in PRAT metabolite effects on the kidney. This study provides a theoretical basis for the use of hypoglycemic drugs combined with vitamin D therapy to improve diabetic nephropathy.