Abstract
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.