Microbiota-driven uric acid reduction by Lactiplantibacillus plantarum 15-5 through nucleoside catabolism and short-chain fatty acid-mediated host protection.

Hyperuricemia, driven by disrupted purine metabolism, predisposes individuals to hepatic and renal injury. To explore potential microbial interventions, 50 lactic acid bacterial (LAB) strains were isolated from Tibetan fermented foods, and 3 nucleoside-degrading candidates were identified, including Lactiplantibacillus plantarum 15-5, Lactiplantibacillus plantarum YL-2, and Lacticaseibacillus paracasei XS23. Strain 15-5 eliminated 99% of inosine and guanosine within 1 h, surpassing YL-2 and XS23. In hyperuricemic mice, L. plantarum 15-5 reduced serum uric acid by 42.91%, normalized hepatic xanthine oxidase activity by 22.57%, restored BUN and creatinine levels toward baseline, and markedly alleviated hepatic and renal tissue damage, while also suppressing proinflammatory cytokines IL-1β and TNF-α. The L. plantarum 15-5 increased fecal short-chain fatty acids, particularly propionate and butyrate (2- to 3-fold), and partially recovered gut microbial diversity and composition under hyperuricemia. Comparative genomics indicated that 15-5 possesses broader metabolic and ecological capacities than YL-2 or XS23, consistent with its superior functional performance. These results reveal a strain-specific framework linking nucleoside catabolism, microbiota-mediated fermentation, and host metabolic and inflammatory regulation, identifying L. plantarum 15-5 as a metabolically versatile candidate for intervention in hyperuricemia and associated hepatic and renal injury.