Lactiplantibacillus plantarum WLPL04 from Human Breast Milk Attenuates Hyperuricemia via Coordinated Purine Salvage Pathway, Renal Transporter Regulation, and Gut Microbiota Remodeling

Oral administration of <i>L. plantarum</i> WLPL04 significantly reduced serum UA level and XOD activity in a dose-dependent manner. Moreover, <i>L. plantarum</i> WLPL04 treatment enhanced UA excretion by upregulating <i>ABCG2</i> and downregulating <i>URAT1</i> and <i>GLUT9</i> expression. It ameliorated renal injury and suppressed inflammation via downregulation of the NLRP3 inflammasome pathway. 16S rRNA gene sequencing revealed that <i>L. plantarum</i> WLPL04 restored gut microbial diversity and promoted the enrichment of beneficial genera such as <i>Bacteroides,</i> which was negatively correlated with UA in serum, creatinine, and inflammatory cytokines. Moreover, transcript analysis revealed upregulation of purine salvage genes (<i>hpt</i> and <i>xpt</i>), suggesting enhanced salvage pathway recycling of purine bases and reduced urate production. Those findings suggest that <i>L. plantarum</i> 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.