Comparative analysis of hyperuricemia induction methods and probiotic interventions in mice

Abstract

Probiotics are widely used as functional food additives, but more studies are needed for their use in mitigation of hyperuricemia (HUA). Currently, there are no standardized animal models for HUA. There is significant variability in the animal strains, drugs, dosages, and modeling periods used in published studies, which greatly impacts the comparability of experimental results and complicates the effectiveness evaluation of therapeutic agents. In this study, we systematically compared different methods for inducing HUA in C57BL/6JNifdc mice and investigated the potential of probiotics to regulate blood uric acid levels. Our results revealed significant differences in blood uric acid levels and renal impairment among the methods. Adenine causes severe renal injury, increases hepatic xanthine oxidase and purine nucleoside phosphorylase activity, and inhibits the expression of uric acid transporter proteins in the kidneys. In contrast, inosine, guanosine, and hypoxanthine mildly induce hyperuricemia in mice. We screened seven probiotic strains from fermented dairy products and evaluated their effects on uric acid metabolism both in vitro and in vivo. Notably, probiotics showed significant potential for degrading uric acid, modulating the expression of uric acid transporter proteins in the kidneys, and inhibiting renal inflammation. These findings provide valuable insights into the pathogenesis of HUA and highlight the therapeutic potential of specific probiotics for managing this metabolic disorder. Our study highlights the importance of selecting appropriate animal models for HUA research and suggests that probiotics can be used as promising functional food additives to assist in hyperuricemia treatment.