Wang Yanbo, Zhang Huijiao, Liu Shujun, Sun Sheng, Ren Weibin, Wang Tao, Zhang Shujuan, Yao Hangping, Jin Changzhong, Wu Nanping
Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, PR China.
Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, PR China.
Curr Res Microb Sci. 2025 Jun 12;9:100422. doi: 10.1016/j.crmicr.2025.100422. eCollection 2025.
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.
益生菌被广泛用作功能性食品添加剂，但它们在缓解高尿酸血症（HUA）方面的应用还需要更多研究。目前，尚无标准化的HUA动物模型。已发表研究中使用的动物品系、药物、剂量和建模周期存在显著差异，这极大地影响了实验结果的可比性，并使治疗药物的有效性评估变得复杂。在本研究中，我们系统地比较了在C57BL/6JNifdc小鼠中诱导HUA的不同方法，并研究了益生菌调节血尿酸水平的潜力。我们的结果显示，不同方法之间血尿酸水平和肾损伤存在显著差异。腺嘌呤会导致严重的肾损伤，增加肝脏黄嘌呤氧化酶和嘌呤核苷磷酸化酶的活性，并抑制肾脏中尿酸转运蛋白的表达。相比之下，肌苷、鸟苷和次黄嘌呤会轻度诱导小鼠高尿酸血症。我们从发酵乳制品中筛选了7种益生菌菌株，并在体外和体内评估了它们对尿酸代谢的影响。值得注意的是，益生菌在降解尿酸、调节肾脏中尿酸转运蛋白的表达以及抑制肾脏炎症方面显示出显著潜力。这些发现为HUA的发病机制提供了有价值的见解，并突出了特定益生菌对管理这种代谢紊乱的治疗潜力。我们的研究强调了为HUA研究选择合适动物模型的重要性，并表明益生菌可作为有前景的功能性食品添加剂用于辅助高尿酸血症治疗。
