Oral Administration of Lacticaseibacillus paracasei SUB12 Alleviated Hyperuricemia via Modulating the SUCNR1/HIF-1α/XOD Axis

Background: The global prevalence of hyperuricemia (HUA) has increased worldwide, and probiotics are considered an adjunctive treatment with fewer side effects. However, the effective strains and underlying mechanisms are not well understood. Objective: This study aimed to investigate the role of Lacticaseibacillus paracasei SUB12 (SUB12) in alleviating HUA and elucidate its potential molecular mechanisms. Methods: In this study, a HUA mouse model was established using potassium oxonate and adenine to evaluate the uric acid-lowering effect of SUB12. High-throughput metabolomics and 16S rRNA sequencing were used to identify key metabolites and altered microbiota. Results: Oral administration of SUB12 significantly reduced serum UA level, hepatic xanthine oxidase (XOD) activity, and renal inflammation and altered uric acid transport-related proteins. Sequencing analysis suggested that SUB12 not only had the capacity of consuming succinate but also reduced the abundance of succinate-producing Prevotellamassilia. Succinate supplementation significantly promoted XOD activity through the succinate receptor 1 (SUCNR1)/hypoxia-inducible factor 1-alpha (HIF-1α) axis. Conclusions: Our findings reveal that SUB12 attenuates hyperuricemia by down-regulating succinate, which promotes XOD activity and uric acid production through the SUCNR1/HIF-1α/XOD axis.