Alginate alleviates hyperuricemia by modulating the Pediococcus acidilactici LW1-1-butyrate-NLRP3 inflammasome axis

Hyperuricemia (HUA) is a prevalent metabolic disorder and a growing global health concern, in which the gut microbiota plays a critical role in uric acid (UA) metabolism. In this study, alginate (Alg; Mw: 60 kDa, G/M = 1.80), a marine-derived polysaccharide composed of α-L-guluronic acid and β-D-mannuronic acid, was investigated for its protective effects against HUA. Alg administration significantly reduced serum UA levels and alleviated HUA-associated body weight loss. Mechanistically, Alg reshaped gut microbial dysbiosis, particularly by selectively enriching lactic acid bacteria. From alginate-treated HUA mice, Pediococcus acidilactici LW1-1 was isolated using a high-UA selective medium. In vivo, P. acidilactici LW1-1 enriched butyrate-producing bacteria and increased butyrate levels, thereby protecting against intestinal inflammation and barrier dysfunction. Both P. acidilactici LW1-1 and butyrate suppressed intestinal inflammation by inhibiting nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation and enhancing tight junction integrity. Concurrently, these interventions upregulated expression of the urate efflux transporter ATP-binding cassette subfamily G member 2 (ABCG2) in the intestine and kidney, thereby promoting UA excretion via dual pathways. Collectively, our findings highlight the therapeutic potential and safety of the polysaccharide-microbiota-metabolite axis in HUA and propose a novel microbiota-targeted strategy for managing HUA through probiotic and prebiotic interventions.