Structure-activity relationship and underlying mechanisms of natural polysaccharides in ameliorating hyperuricemia via targeting gut microbiota.

Hyperuricemia (HUA), a common metabolic disorder, is associated with multiple diseases and imposes an increasing burden on public health. Current pharmacological therapies are often limited by single-target effects and potential adverse reactions. Recent evidence suggests that the intestine contributes to urate homeostasis, with the gut microbiota and intestinal urate transporters involved in extra-renal urate handling. Natural polysaccharides have attracted increasing attention as potential microecological modulators because of their urate-lowering and metabolic regulatory activities. Accumulating studies suggest that natural polysaccharides may alleviate HUA by reshaping gut microbial composition, regulating microbial metabolite production, and improving intestinal barrier integrity. However, the mechanisms by which polysaccharides modulate HUA through the gut microbiota have not been systematically summarized. Therefore, this review synthesizes the relationship between intestinal dysbiosis and HUA and further discusses the potential relationships between the structural characteristics of natural polysaccharides and their gut microbiota-modulating effects. Moreover, the possible mechanisms by which polysaccharides regulate urate metabolism through the gut microbiota and microbial metabolites are analyzed, and the advantages of polysaccharide-based drug delivery systems are discussed. This review provides a basis for microbiota-targeted intervention in HUA and the development of polysaccharide-based formulations.