Peptidoglycan from Lactiplantibacillus plantarum YC Alleviates Hyperuricemia via the "Microbiota-Gut-Kidney" Axis: Structural Characterization and Metabolic Regulation.

Hyperuricemia (HUA) is a prevalent metabolic disorder necessitating safe and effective interventions. Although probiotics demonstrate potential in HUA management, the specific contributions of their cellular components remain unexplored. In this study, peptidoglycan (PGN) isolated from Lactiplantibacillus plantarum YC was characterized as an A1γ-type chemotype (l-Ala-d-iGln-mDAP-d-Ala) via amino acid analysis, FTIR, NMR, and MALDI-TOF MS. In HUA mice, oral PGN significantly reduced serum uric acid, creatinine, and blood urea nitrogen levels. Mechanistically, PGN inhibited hepatic xanthine oxidase activity and transcriptionally remodeled the urate transport machinery by upregulating renal ABCG2/OAT1 and colonic ABCG2 expression, while downregulating renal URAT1/GLUT9 and colonic GLUT9 expression. Furthermore, PGN attenuated systemic inflammation by lowering TNF-α, IL-1β, and IL-6. Integrative multiomics revealed that PGN remodeled gut microbiota, notably enriching Muribaculaceae and Bacteroides, and modulated purine and amino acid metabolism. These findings identify L. plantarum YC-derived PGN as a promising postbiotic candidate for targeted HUA intervention via the microbiota-gut-kidney axis.