Unveiling the molecular secrets: How <em>Levilactobacillus brevis</em> PDD-5 lowers uric acid levels

A high-purine diet readily induces hyperuricemia, whereas certain lactic acid bacteria (LAB) can absorb and metabolize purines, thereby modulating uric acid levels. However, studies elucidating the molecular mechanisms by which lactic acid bacteria lower uric acid levels remain limited. In this study, we investigated<em> Levilactobacillus brevis</em> PDD-5, a strain previously shown to alleviate hyperuricemia through efficient purine absorption. Comprehensive metabolic and transcriptomic analyses were performed to compare <em>L. brevis</em> PDD-5 with a non-uric-acid-lowering strain. Using HPLC–MS/MS–based targeted metabolomics, we identified significant differences in purine nucleoside degradation between the two strains. Transcriptomic profiling revealed that<em> L. brevis</em> PDD-5 activates purine catabolism <em>via </em>upregulation of the <em>deoD </em>gene, which encodes purine nucleoside phosphorylase, thereby facilitating nucleoside-to-base conversion. Xanthine served as a key substrate promoting the<em> de novo </em>purine synthesis pathway and remained active under purine-rich conditions, likely because of transcriptional derepression of the<em> purR</em> regulator. These findings elucidate the molecular framework of the uric acid–lowering mechanism of<em> L. brevis</em> PDD-5 and provide a theoretical foundation for the development of safe, effective LAB-based interventions against hyperuricemia.