Astragalus polysaccharides prevent kidney stone formation in an ethylene glycol-induced rat model via modulation of gut microbiota and short-chain fatty acid production.

Kidney stones are a common urological disorder associated with significant pain and renal complications. Astragalus polysaccharides (APS) are a bioactive component of Traditional Chinese Medicine that has shown therapeutic potential in renal disorders, potentially through the modulation of the gut microbiota and its metabolites. Based on its properties, it was hypothesized that APS could prevent kidney stone formation by modulating gut microbiota and altering short-chain fatty acid (SCFA) production. In this study, an ethylene glycol-induced rat model was used to investigate APS's effects on kidney stone formation, renal injury, gut microbiome composition, and targeted SCFAs metabolomics. APS treatment significantly reduced calcium oxalate crystal deposition and urinary oxalate levels, alleviated renal tissue damage, and regulated key bacterial taxa involved in oxalate metabolism and SCFA production, particularly restoring serum butyric acid levels. Sodium butyrate supplements further enhanced the protective function of APS in kidney stones. Fecal microbiota transplantation (FMT) results revealed that antibiotic-depleted recipients of microbiota from healthy mice donors or APS-treated mice donors exhibited improved renal function compared with recipients of stone microbiota. These findings support that APS prevents kidney stone formation by modulating the gut-kidney axis through microbiota and metabolite changes, with FMT demonstrating the functional contribution of gut microbial communities to disease outcomes. Therefore, APS represents a promising natural therapeutic approach for kidney stone prevention and highlights the relevance of microbiota-based strategies in managing kidney stones.