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Exploring the gut-kidney axis: Berberine's role in alleviating chronic kidney disease through microbiota and short-chain fatty acids

Lu Z, Li Z, Gu S, Cai Y, Wu Y, Huang L, Yu Y, Liu X et al.

Journal of ethnopharmacology, 2026

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Berberine (BBR), a compound widely used in traditional Chinese medicine, has been recognized for its therapeutic effects on chronic kidney disease (CKD), primarily by modulating the gut microbiota. However, further research is needed to fully understand the mechanisms underlying its beneficial effects.

AIM OF THE STUDY: This study aims to explore the renoprotective effects of BBR through the modulation of gut microbiota and regulation of short-chain fatty acids (SCFAs).

METHODS: In Part I, a CKD mouse model was established using a diet containing 0.2 % adenine for six weeks. Mice were divided into four groups: Normal, Adenine-induced (Ade), and BBR-treated (BBR-L and BBR-H). Renal function was assessed by serum creatinine (SCR) and blood urea nitrogen (BUN). Histological damage was analyzed using staining techniques, and intestinal barrier function was evaluated by measuring Mucin 2 (MUC-2) expression and serum Diamine Oxidase (DAO) and D-lactic acid (D-LA). Gut microbiota composition was analyzed via 16S rRNA sequencing, while SCFA levels were quantified by UHPLC-MRM-MS. Then, the expression of G Protein-Coupled Receptors (GPRs) related to SCFAs in kidney were detected. In Part II, gut microbiota depletion using antibiotics was conducted to examine whether the effects of BBR on kidney injury and intestinal barrier depend on gut microbiota modulation.

RESULTS: BBR supplementation significantly reduced SCR and BUN levels in adenine-induced mice…

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