Fucoidan-driven Bacteroides xylanisolvens HS-1 alleviates hyperuricemia by promoting intestinal uric acid excretion via the PPARγ/ABCG2 signaling pathway.

The rising prevalence of hyperuricemia and associated complications present a substantial global health challenge. Fucoidan, a natural sulfate-rich polysaccharide degraded by gut microbiota, is under investigation as a potential therapeutic agent for reducing uric acid levels. However, the precise mechanism underlying its effects remains unclear. Herein, fucoidan intervention markedly decreased uric acid levels by modulating the composition of gut microbiota, particularly by promoting the colonization of Bacteroides and increasing the intestinal inosine content. Furthermore, in vitro anaerobic fermentation was used to screen the fucoidan-driven strain Bacteroides xylanisolvens HS-1, enabling functional characterization. Supplementation with B. xylanisolvens HS-1 influenced purine metabolism by increasing intestinal inosine levels while maintaining stable serum inosine concentrations. It also enriched the ATP-binding cassette (ABC) transporter pathway and alleviated hyperuricemia-induced intestinal dysfunction. Mechanistically, B. xylanisolvens HS-1 activated the upstream signaling molecule PPARγ, promoting intestinal uric acid excretion and enhancing barrier function by upregulating ABC superfamily G member 2 and MUC2 expression. This study delineates the role of the polysaccharide-gut microbiota axis in modulating urate homeostasis, revealing the anti-hyperuricemic effects of natural bioactive compounds through microbial metabolism.