Host-derived Lactobacillus plantarum alleviates hyperuricemia by improving gut microbial community and hydrolase-mediated degradation of purine nucleosides

宿主来源的植物乳杆菌通过改善肠道微生物群落和水解酶介导的嘌呤核苷降解来缓解高尿酸血症

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作者:Yang Fu, Xiao-Dan Luo, Jin-Ze Li, Qian-Yuan Mo, Xue Wang, Yue Zhao, You-Ming Zhang, Hao-Tong Luo, Dai-Yang Xia, Wei-Qing Ma, Jian-Ying Chen, Li-Hau Wang, Qiu-Yi Deng, Lukuyu Ben, Muhammad Kashif Saleemi, Xian-Zhi Jiang, Juan Chen, Kai Miao, Zhen-Ping Lin, Peng Zhang, Hui Ye, Qing-Yun Cao, Yong-Wen Z

Abstract

The gut microbiota is implicated in the pathogenesis of hyperuricemia (HUA) and gout. However, it remains unclear whether probiotics residing in the host gut, such as Lactobacillus, can prevent HUA development. Herein, we isolated Lactobacillus plantarum SQ001 from the cecum of HUA geese and conducted in vitro assays on uric acid (UA) and nucleoside co-culture. Metabolomics and genome-wide analyses, revealed that this strain may promote nucleoside uptake and hydrolysis through its nucleoside hydrolase gene. The functional role of iunH gene was confirmed via heterologous expression and gene knockout studies. Oral administration of L. plantarum SQ001 resulted in increased abundance of Lactobacillus species and reduced serum UA levels. Furthermore, it downregulated hepatic xanthine oxidase, a key enzyme involved in UA synthesis, as well as renal reabsorption protein GLUT9, while enhancing the expression of renal excretion protein ABCG2. Our findings suggest that L. plantarum has potential to ameliorate gut microbial dysbiosis with HUA, thereby offering insights into its potential application as a probiotic therapy for individuals with HUA or gout.

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