Abstract
BACKGROUND: Hyperuricemia (HUA), a metabolic disorder characterized by high serum uric acid (UA) level, presents a growing global health challenge. METHOD: In this study, a stable murine model of HUA was established by orally administering adenine (100 mg/kg) and potassium oxonate (600 mg/kg) in C57BL/6J mice, resulting in significant elevation of serum UA and xanthine oxidase (XOD) activity, as well as renal pathological alterations. Given the anti-hyperuricemia potential of Lactiplantibacillus plantarum WLPL04, a strain from a human breast milk was evaluated. CONCLUSIONS: Oral administration of L. plantarum WLPL04 significantly reduced serum UA level and XOD activity in a dose-dependent manner. Moreover, L. plantarum WLPL04 treatment enhanced UA excretion by upregulating ABCG2 and downregulating URAT1 and GLUT9 expression. It ameliorated renal injury and suppressed inflammation via downregulation of the NLRP3 inflammasome pathway. 16S rRNA gene sequencing revealed that L. plantarum WLPL04 restored gut microbial diversity and promoted the enrichment of beneficial genera such as Bacteroides, which was negatively correlated with UA in serum, creatinine, and inflammatory cytokines. Moreover, transcript analysis revealed upregulation of purine salvage genes (hpt and xpt), suggesting enhanced salvage pathway recycling of purine bases and reduced urate production. Those findings suggest that L. plantarum WLPL04 exerted multi-targeted anti-hyperuricemia effects through coordinated regulation of host purine metabolism, urate transport, inflammation, and gut microbiota composition, providing a promising probiotic candidate for HUA management.