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 Levilactobacillus brevis PDD-5, a strain previously shown to alleviate hyperuricemia through efficient purine absorption. Comprehensive metabolic and transcriptomic analyses were performed to compare L. brevis 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 L. brevis PDD-5 activates purine catabolism via upregulation of the deoD gene, which encodes purine nucleoside phosphorylase, thereby facilitating nucleoside-to-base conversion. Xanthine served as a key substrate promoting the de novo purine synthesis pathway and remained active under purine-rich conditions, likely because of transcriptional derepression of the purR regulator. These findings elucidate the molecular framework of the uric acid–lowering mechanism of L. brevis PDD-5 and provide a theoretical foundation for the development of safe, effective LAB-based interventions against hyperuricemia.
Xu et al. (2026) studied this question.