A Post-NGP Mitsuokella jalaludinii as a Therapeutic Candidate for Gout.

Gout is a common inflammatory disease closely associated with hyperuricemia, and its global prevalence is increasing, highlighting the need for safer and more effective therapeutic strategies. Recently, microbiome-based therapeutics have emerged as promising alternatives, and the development of functionally validated NGP and their advanced forms, post-NGP strains, is gaining increasing attention. In this study, microbiome-derived bacterial strains were screened based on their in vitro uric acid (UA)-reducing capacity and hypoxanthine utilization. Among the tested strains, Mitsuokella jalaludinii exhibited the most pronounced uric acid reduction and growth enhancement in response to purine substrates compared to conventional lactic acid bacteria. This strain reduced uric acid levels by approximately 30% after 48 h (p < 0.001) and showed significantly increased growth in purine-enriched minimal medium (p < 0.01). WGS further confirmed its strain-level novelty, leading to its designation as PMC73, and revealed the presence of genetic features associated with purine metabolism and UA regulation. In a MSU-induced RAW 264.7 macrophage model, PMC73 significantly reduced UA levels (p < 0.001) and modulated immune responses by increasing anti-inflammatory cytokines while decreasing pro-inflammatory cytokines. These effects were associated with suppression of the NLRP3-caspase-1, along with downregulation of URAT1 and XOD, indicating coordinated regulation of uric acid production, reabsorption, and inflammatory pathways. Based on safety evaluation, including d-lactate production, cytotoxicity assays and oral toxicity assessment in a mouse model, demonstrated that PMC73 exhibited no pathogenic or toxic properties. Therefore, PMC73 represents a promising microbiome-based candidate with relevance to gout-associated hyperuricemia, warranting further in vivo and clinical investigations.