Diabetes Obes Metab. 2026 Aug 18. doi: 10.1111/dom.71245. Online ahead of print.
ABSTRACT
AIMS: Diabetic kidney disease (DKD) is one of the main causes of kidney failure worldwide. Interestingly, patients affected by DKD are characterised by a low abundance of gut bacteria producing short fatty acids including butyrate, which is suggested to play a role in the decline of renal function. Consequently, we aimed to test the effects of oral butyrate supplementation on kidney health in mice affected by DKD.
MATERIAL AND METHODS: To this end, we treated diabetic BKS db/db mice (C57BLKS/J Leprdb) via drinking water with the eNOS inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME), which accelerates the progression of DKD. Simultaneously, mice were fed low-fat chow with or without 5% butyrate.
RESULTS: Oral butyrate supplementation reduced mesangial expansion, glomerular enlargement and medullary fibrosis in kidney biopsies of the mice. These protective effects correlated with an increased abundance of Akkermansiaceae in the gut. In mice treated with butyrate, the abundance of Akkermansiaceae positively correlated with glomerular filtration rate (GFR) and plasma concentration of indole-3-methyl acetate and indole-3-acetaldehyde, key metabolites associated with many beneficial cardiovascular effects.
CONCLUSIONS: In conclusion, oral butyrate supplementation in mice with DKD improves kidney morphology, accompanied by an increased abundance of Akkermansiaceae in the gut. Future studies, such as transplantation of Akkermansia, should reveal whether this relationship is causal and translate into improved kidney function in DKD.
PMID:42613310 | DOI:10.1111/dom.71245