Uric Acid-Degrading Lacticaseibacillus paracasei CPU202306 Ameliorates Hyperuricemia by Regulating Uric Acid Metabolism and Intestinal Microecology in Mice.

Hyperuricemia, characterized by elevated levels of uric acid in the blood, poses a significant health threat due to its association with various adverse health outcomes, and lactic acid bacteria from the gut microbiota may offer solutions. Our investigation focused on Lacticaseibacillus paracasei CPU202306, isolated from fermented pickles for its potent uric acid degradation and probiotic properties. This bacterium effectively reduced blood uric acid levels by breaking down uric acid and inhibiting hepatic xanthine oxidase (XOD) and adenosine deaminase (ADA) enzymes. Additionally, it stimulated the production of short-chain fatty acid (SCFAs) in the colon, enhancing the expression of uric acid secretion transport proteins (ATP-binding cassette sub-family G member 2 and organic anion transporter 3) while suppressing absorption transport proteins (glucose transporter 9 and uric acid transporter 1). This orchestrated process promoted uric acid excretion. L. paracasei CPU202306 also improved gut microbiota health by reinforcing tight junction proteins, shifting the microbiota to a healthier composition, and reducing harmful bacteria. This transformation inhibited kidney TLR4/MyD88/NF-κB inflammatory signaling, leading to a significant decrease in pro-inflammatory cytokines and an increase in anti-inflammatory cytokines, mitigating kidney inflammation. Furthermore, the bacterium supported kidney health by influencing amino acid metabolic pathways linked to the gut-kidney axis. In summary, our study highlights the diverse mechanisms through which L. paracasei CPU202306 addresses hyperuricemia, showcasing its therapeutic potential for this condition.