Screening polysaccharides with the capacity to improve the gut microbial degradation of uric acid for hyperuricemia treatment

Abstract Hyperuricemia is closely linked to gut microbiota dysbiosis, characterized by a reduced capacity for microbial uric acid degradation. However, strategies to restore this intestinal urate-metabolizing function remain underexplored. In this study, we screened six dietary polysaccharides in vitro and identified sodium alginate as the most effective candidate for promoting microbial uric acid degradation. Metagenomic analysis of fermentation broth revealed that sodium alginate specifically enriched uricolytic species including Anaerostipes caccae, Dorea formicigenerans, Clostridium sp., and Enterococcus faecalis. In hyperuricemic mice, sodium alginate significantly lowered serum uric acid levels and provided renal and hepatic protection. Mechanistically, sodium alginate remodeled the gut ecosystem by boosting urate-metabolizing taxa such as Blautia, Collinsella, and Alistipes while upregulating the intestinal transporter ABCG2. Notably, fecal uric acid levels decreased despite increased intestinal secretion, confirming that sodium alginate promotes microbial decomposition rather than simple excretion. These findings establish sodium alginate as a safe and sustainable prebiotic for managing hyperuricemia. Moreover, they offer a novel screening strategy for identifying effective polysaccharides based on their ability to restore the host's intestinal urate-degrading capacity.