Host-derivedLactobacillus plantarumalleviates hyperuricemia by improving gut microbial community and hydrolase-mediated degradation of purine nucleosides

Author:

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

Abstract

AbstractGut microbiota has been considered to be associated with the development of hyperuricemia (HUA) and gout. Some prebiotics from different sources had the potential alleviation function in HUA. However, whether host-derived potential probiotics, like Lactobacillus, from the gut of HUA animals could prevent the development of HUA is still uncertain.In this study, we established a HUA geese model and isolated aLactobacillus plantarumstrain, SQ001, from the cecum of HUA geese. Nucleoside co-culture and metabolomics analyses revealed thatL. plantarumSQ001 is involved in the absorption and hydrolysis of nucleosides. Whole genome analysis showed there are four genes related with nucleosides hydrolysis inL. plantarumSQ001. The function of iunH, a nucleoside hydrolase gene, was further confirmed by heterologous expression and knockout assays. Oral administration ofL. plantarumSQ001 in HUA geese models upregulated theLactobacillusabundance and reduced serum uric acid (UA) levels. Likewise, in mouse models,L. plantarumSQ001 increased theL. plantarumabundance and lowered serum UA levels by reducing hepatic UA synthesis protein XO and renal UA reabsorption protein GLUT9 expression, while increasing renal UA excretion protein ABCG2 expression.Our findings demonstrated that host-derived probiotics from geese could alleviate gut microbe dysbiosis and HUA in its host and mouse model. This study provides insights into the potential probiotic role ofLactobacillus plantarumin HUA or gout therapy.Graphical abstract

Publisher

Cold Spring Harbor Laboratory

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