Poricoic Acid A Protects Against High-Salt-Diet Induced Renal Fibrosis by Modulating Gut Microbiota and SCFA Metabolism

Abstract

The gut microbiota serves a critical role in the development of chronic kidney disease (CKD). High salt intake has been known to cause hypertension and CKD, however, it is still unclear whether it also affects gut microbiota in CKD mice. This article first studied the salutary effects of poricoic acid A (PAA), a natural triterpenoid from Poria cocos, on high salt diet-induced CKD in kunming mice. It was demonstrated that the administration of PAA by oral gavage (20 mg/kg·bw) could decrease the kidney index and urinary protein levels, prevent the kidney tubule dilated and renal fibrosis, and activated the expression of adenosine monophosphate-activated protein kinase (AMPK) in kidney. In addition, 16 S rRNA-based microbiota analysis indicated that PAA ameliorated intestinal microbiota dysbiosis caused by high-salt-diet and particularly enhanced the abundances of beneficial microbiota, such as Lactobacillus and Akkermansia, followed by a significant increase in the levels of short-chain fatty acids (SCFAs). Meanwhile, PAA improved intestinal barrier damage and increased the expression of intestinal tight junction protein. In summary, these experiments demonstrated that PAA enhances the growth of probiotics while decreasing the abundance of endotoxin-producing bacteria. This dual action contributes to the amelioration of intestinal mucosal barrier dysfunction and mitigates the impact of a high-salt diet on renal interstitial fibrosis in mice.

Keywords: AMPK; Gut microbiota; High salt diet; Renal fibrosis; SCFAs.