Limosilactobacillus reuteri Urob-7 Alleviates Hyperuricemia by Modulating Uric Acid Metabolism Through Nucleoside Degradation and Xanthine Oxidase Inhibition

Hyperuricemia (HUA), a metabolic disorder characterized by elevated serum uric acid resulting from imbalanced production and excretion, is associated with gout and other serious health issues. This study aimed to screen out the potential probiotics with HUA-alleviating properties among 20 <i>Lactobacillus</i> strains. The results showed that <i>L. reuteri</i> Urob-7 exhibited the highest degradation rates for inosine and guanosine (82.10% and 88.78%, respectively) and strong xanthine oxidase (XOD) inhibitory activity (62.86%). In a HUA mouse model induced by inosine, guanosine, and potassium oxonate, <i>L. reuteri</i> Urob-7 intervention significantly reduced serum uric acid levels by 46.54%, restoring them to levels similar to control groups, and improved kidney function indicators. Moreover, Urob-7 reduced hepatic XOD activity by 37.6% and downregulated XOD expression in the intestines, decreasing excessive uric acid synthesis. It also significantly inhibited the NF-κB/NLRP3 inflammatory pathway, reducing the expression levels of <i>NF-κB</i> and <i>NLRP3</i> in the kidneys by 39.3% and 47.6%, respectively. Furthermore, <i>L. reuteri</i> Urob-7 increased the abundance of short-chain fatty acid-producing bacteria (e.g., <i>Ruminococcus</i> and <i>Intestinimonas</i>) while reducing the proportion of pathogenic bacteria (e.g., <i>Bacteroides</i> and <i>Anaerovorax</i>), thus ameliorating gut microbiota dysbiosis and intestinal barrier dysfunction. In summary, <i>L. reuteri</i> Urob-7 effectively relieved HUA by modulating uric acid metabolism, suppressing inflammation, and improving gut microbiota balance. These results highlighted its potential as a promising candidate for HUA.