Hyperuricemia is a metabolic disorder caused by increased uric acid (UA) synthesis or decreased UA excretion. Changes in eating habits have led to an increase in the consumption of purine-rich foods, which is closely related to hyperuricemia. Therefore, decreased purine absorption, increased UA excretion, and decreased UA synthesis are the main strategies to ameliorate hyperuricemia. This study aimed to screen the lactic acid bacteria (LAB) with purine degrading ability and examine the serum UA-lowering effect in a hyperuricemia mouse model. As a result, Lacticaseibacillus paracasei MJM60396 was selected from 22 LAB isolated from fermented foods for 100% assimilation of inosine and guanosine. MJM60396 showed probiotic characteristics and safety properties. In the animal study, the serum uric acid was significantly reduced to a normal level after oral administration of MJM60396 for 3 weeks. The amount of xanthine oxidase, which catalyzes the formation of uric acid, decreased by 81%, and the transporters for excretion of urate were upregulated. Histopathological analysis showed that the damaged glomerulus, Bowman’s capsule, and tubules of the kidney caused by hyperuricemia was relieved. In addition, the impaired intestinal barrier was recovered and the expression of tight junction proteins, ZO-1 and occludin, was increased. Analysis of the microbiome showed that the relative abundance of Muribaculaceae and Lachnospiraceae bacteria, which were related to the intestinal barrier integrity, was increased in the MJM60396 group. Therefore, these results demonstrated that L. paracasei MJM60396 can prevent hyperuricemia in multiple ways by absorbing purines, decreasing UA synthesis by suppressing xanthine oxidase, and increasing UA excretion by regulating urate transporters.

Hyperuricemia is a metabolic disorder characterized by elevated serum uric acid levels and is increasingly linked to alterations in intestinal mucosal condition and gut microbiota composition. Probiotics have been proposed as safe, non-pharmacological approaches for managing hyperuricemia, but strain-specific evidence remains limited. This study aimed to evaluate the anti-hyperuricemic potential of Limosilactobacillus reuteri MBHC10138, isolated from human breast milk, and to examine its association with purine metabolism–related parameters, renal morphological features, intestinal barrier-associated markers, and gut microbiota composition. In vitro, MBHC10138 effectively degraded purine nucleosides that are metabolized into uric acid, suggesting its potential to reduce uric acid production in the host. In a mouse model of diet- and oxonate-induced hyperuricemia, oral administration of MBHC10138 significantly lowered serum uric acid levels to a level comparable with allopurinol treatment, while improving renal morphology. Histological and molecular analyses demonstrated restoration of the tight junction proteins zonula occludens-1 and occludin, indicative of enhanced intestinal barrier integrity. Furthermore, MBHC10138 administration modulated the gut microbiota by restoring microbial α-diversity and significantly increasing the relative abundances of the Clostridia vadinBB60 group and Oscillospiraceae, taxa associated with butyrate production, compared with the allopurinol-treated group. Collectively, these findings indicate that MBHC10138 exerts dual actions against hyperuricemia and intestinal barrier dysfunction through the regulation of purine metabolism, promotion of renal urate excretion, and modulation of gut microbial composition. MBHC10138 may thus represent a promising probiotic candidate for the prevention and adjunctive management of hyperuricemia-related metabolic disorders.