Empowering probiotics with high xanthine transport for effective hyperuricemia management
Zhen-Ping Zou,
Ju-Ling Li,
Yi-Fan Zhang,
Ying Zhou,
Bang-Ce Ye
Affiliations
Zhen-Ping Zou
Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, Institute of Engineering Biology and Health, East China University of Science and Technology, Shanghai, China
Ju-Ling Li
Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, Institute of Engineering Biology and Health, East China University of Science and Technology, Shanghai, China
Yi-Fan Zhang
Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, Institute of Engineering Biology and Health, East China University of Science and Technology, Shanghai, China
Ying Zhou
Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, Institute of Engineering Biology and Health, East China University of Science and Technology, Shanghai, China
Bang-Ce Ye
Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, Institute of Engineering Biology and Health, East China University of Science and Technology, Shanghai, China
Hyperuricemia, a prevalent metabolic disorder, poses a susceptibility to various complications. The conventional pharmacotherapeutic approaches for hyperuricemia often entail notable adverse effects, posing substantial clinical challenges. Hence, the imperative lies in the development of novel, safe and effective strategies for preventing and treating hyperuricemia. Here, we developed a probiotic Escherichia coli Nissle 1917 strain, designated as YES301, which contains a rationally designed xanthine importer XanQ, enabling efficient uptake of xanthine and hypoxanthine, consequently leading to reduced serum uric acid concentrations and amelioration of renal impairments in a murine model of hyperuricemia. Importantly, YES301 exhibited a therapeutic efficacy comparable to allopurinol, a conventional uric acid-lowering agent, and manifesting fewer adverse effects and enhanced biosafety. These findings highlight the promising potential of engineered probiotics in the management of hyperuricemia through reducing intestinal purine levels.
