Uric Acid-Reducing Potential of Limosilactobacillus Fermentum FOSU YHD19: A Comprehensive Genomic and Phenotypic Study.

The escalating global burden of hyperuricemia, driven by modern dietary patterns and sedentary lifestyles, has prompted urgent exploration of novel therapeutic strategies, with particular emphasis on developing targeted probiotic interventions as a potential alternative to conventional pharmacological approaches. This study successfully isolated Limosilactobacillus fermentum FOSU YHD19 from fermented foods, demonstrating remarkable in vitro uric acid reduction of 12.90% along with high-level degradation of nucleosides. A comprehensive safety evaluation confirmed the absence of harmful enzymatic activities (including nitroreductase, decarboxylase and tryptophanase), hemolytic properties, or antibiotic resistance. The strain exhibited strong stress tolerance, surviving in acidic conditions (pH 2.0), with exposure to gastric juice, and when in the presence of 0.1% bile salts. Additionally, YHD19 demonstrated potent antibacterial activity against multiple pathogenic strains, including E coli, S. aureus, L. monocytogenes, and S. enteritidis. Genomic analysis revealed three nucleoside hydrolases and six transporter systems that collectively facilitate the hypouricemic activity. By ruling out the presence of key uric acid-synthesizing enzymes (xanthine dehydrogenase/oxidase and guanine deaminase), we can attribute the hypouricemic effect primarily to a nucleoside-scavenging mechanism. In addition, the genome harbors 91 stress-responsive genes implicated in acid/base adaptation, thermal shock response, and oxidative defense mechanisms, underscoring the strain's resilience under gastrointestinal stresses. These findings position YHD19 as a safe and effective probiotic candidate for functional foods aimed at managing hyperuricemia, supporting its safety profile for potential probiotic applications.