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

## TL;DR

A specific probiotic, L. reuteri Urob-7, reduces high uric acid levels by breaking down uric acid precursors and reducing inflammation in mice.

## Contribution

L. reuteri Urob-7 is shown to alleviate hyperuricemia through nucleoside degradation, XOD inhibition, and gut microbiota modulation.

## Key findings

- L. reuteri Urob-7 reduced serum uric acid levels by 46.54% in a mouse model of hyperuricemia.
- The probiotic inhibited XOD activity by 37.6% and downregulated XOD expression in the intestines.
- Urob-7 improved gut microbiota balance and reduced inflammation via the NF-κB/NLRP3 pathway.

## Abstract

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 Lactobacillus strains. The results showed that L. reuteri 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, L. reuteri 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 NF-κB and NLRP3 in the kidneys by 39.3% and 47.6%, respectively. Furthermore, L. reuteri Urob-7 increased the abundance of short-chain fatty acid-producing bacteria (e.g., Ruminococcus and Intestinimonas) while reducing the proportion of pathogenic bacteria (e.g., Bacteroides and Anaerovorax), thus ameliorating gut microbiota dysbiosis and intestinal barrier dysfunction. In summary, L. reuteri 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.