A Novel Strategy in Managing Spent Probiotic Culture Media: Metabolome Identified Functional Candidates Against Hyperuricemia

With the rapid expansion of the probiotics industry, the management of spent culture media has emerged as a pressing concern. However, it also represents a potential resource for functional food development. In this study, we investigated and screened anti-hyperuricemia (HUA) metabolites of Lactobacillus paracasei (LP) from spent media (META). Administration of META significantly reduced serum uric acid (UA) (SUA) levels ( p < 0.05), improved kidney function, and alleviated inflammatory infiltration. Furthermore, META modulated UA metabolism by regulating key enzymes (xanthine oxidase [XOD] and adenosine deaminase [ADA]) and urate transporters (organic anion transporter 3 [OAT3], glucose transporter 9 [GLUT9], and urate transporter 1 [URAT1]), while mitigating HUA-induced inflammation through the Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway. To identify bioactive compounds, untargeted metabolomics based on UHPLC-QTOF-MS/MS detected 361 upregulated metabolites. Network pharmacology and molecular docking (MD) analyses further highlighted potential candidates, including 2-isopropylmaleate and ricinoleic acid methyl ester. Collectively, these findings suggest that probiotic culture media waste may serve as a promising natural source for the development of anti-HUA functional foods. Further studies are warranted to assess the bioavailability and efficacy of these metabolites both in vitro and in vivo.