Safety Evaluation of Human-Derived Uric Acid Degrading Lacticaseibacillus paracasei M2a and Its Impact on Gut Microbiota

We report the identification of a human-derived uric acid (UA)-degrading bacterial strain, analyzed its degradation efficiency, and assessed its safety to provide a scientific basis for future clinical applications in the treatment of hyperuricemia (HUA) and gout. Here, we isolated the M2a strain from feces of healthy young men. The strain was identified as Lacticaseibacillus paracasei (formerly Lactobacillus paracasei) via 16S rRNA and biochemical analyses. The in vitro and in vivo efficiencies of M2a uric acid degradation were found to be 45.53% and up to 47.88%, respectively. Strain M2a exhibited no detectable pathogenicity, demonstrated robust tolerance to simulated gastrointestinal conditions, and displayed a favorable safety profile. The strain ameliorated hyperuricemia-associated liver and kidney dysfunction, as evidenced by improved biochemical markers (ALT, AST, BUN, and CRE; P < 0.05) and histopathological findings showing reduced inflammatory cell infiltration and preserved tissue architecture in HE-stained liver and kidney sections. Furthermore, it regulated intestinal microbiota in HUA mice, increased the relative content of beneficial bacteria (e.g., Lacticaseibacillus) in the mouse intestine, and reduced the intestinal presence of Klebsiella and Blautia in mice. Further study of M2a is warranted to elucidate pathways for lowering blood levels of uric acid via clinical utilization of probiotic and associated biologic interventions.