Oral Butyrate Reduces Progression of Kidney Damage in an L-NAME-Induced Diabetic Kidney Disease Mouse Model.

Authors

Maria Novella Nicese, Angela Koudijs, Reshma Lalai, Cristina Avramut, Rico J E Derks, Elena Sánchez-López, Martin Giera, Amanda C M Pronk, Artemiy Kovynev, Sander Kooijman, Patrick C N Rensen, Roel Bijkerk, Bernard M van den Berg, Joris I Rotmans

Published in

Diabetes, obesity & metabolism. Aug 18, 2026. Epub Aug 18, 2026.

Abstract

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.
To this end, we treated diabetic BKS db/db mice (C57BLKS/J Lepr^db) 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.
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.
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
Bibliographic data and abstract were imported from PubMed on 19 Aug 2026.

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