Resveratrol improves diabetic kidney disease by modulating the gut microbiota-short chain fatty acids axis in db/db mice

Abstract

Diabetic kidney disease is associated with the dysbiosis of the gut microbiota and its metabolites. db/db mice were fed chow diet with or without 0.4% resveratrol for 12 weeks, after which the gut microbiota, faecal short-chain fatty acids (SCFAs), and renal fibrosis were analysed. Resveratrol ameliorated the progression of diabetic kidney disease and alleviated tubulointerstitial fibrosis. Further studies showed that gut microbiota dysbiosis was modulated by resveratrol, characterised by the expansion of SCFAs-producing bacteria Faecalibaculum and Lactobacillus, which increased the concentrations of SCFAs (especially acetic acid) in the faeces. Moreover, microbiota transplantation experiments found that alteration of the gut microbiota contributed to the prevention of diabetic kidney disease. Acetate treatment ameliorated proteinuria, glomerulosclerosis and tubulointerstitial fibrosis in db/db mice. Overall, resveratrol improved the progression of diabetic kidney disease by suppressing tubulointerstitial fibrosis, which may be involved, at least in part, in the regulation of the gut microbiota-SCFAs axis.

Keywords:

• Resveratrol
• diabetic kidney disease
• gut microbiota
• short-chain fatty acids

Author contributions

H.Y. and Y.Z. contributed equally to this work. H.Y., Y.Z., J.Y. and S.H. conducted experiments, data acquisition, statistical analysis and the interpretation of the results. X.L., J.H. and F.Z. were responsible for providing information and advice on the data synthesis and analysis. C.C., H.R. and S.Z. contributed to the concept and design of the study, provided guidance during study selection, data analysis, draft development and final submission. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The sequences reported in this paper have been deposited in the NCBI database (accession number PRJNA1001059).

The data are available from the corresponding author on reasonable request.

Additional information

Funding

This study was supported in part by Postdoctoral Research Project by Administration Human Resources and Social Security of Chongqing (2021XM3104), China Postdoctoral Science Foundation (2022MD713712), Natural Science Foundation of Chongqing of China (CSTB2022NSCQ-BHX0013), Project of Chongqing Medical Talent Studio (2022), Program of Chongqing Medical University for Youth Innovation in Future Medicine (W0085), Research Project of Chongqing Education Commission (KJQN202200433) and Program of The Third Affiliated Hospital of Chongqing Medical University (KY22040).