Haina Wang1, Lu Mei2, Ying Deng3, Yinhui Liu3, Xiaoqing Wei3, Man Liu3, Jiaorui Zhou3, Hong Ma3, Pengyuan Zheng2, Jieli Yuan3, Ming Li4. 1. Department of Hematology, Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational Medicine, Second Hospital of Dalian Medical University, Dalian, China; Center for molecular medicine, School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China. 2. Department of Gastroenterology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 3. College of Basic Medical Sciences, Dalian Medical University, Dalian, China. 4. College of Basic Medical Sciences, Dalian Medical University, Dalian, China. Electronic address: vivianmarat@163.com.
Abstract
OBJECTIVE: High fructose consumption exacerbates purine degradation and intestinal dysbiosis, which are closely related to the development of hyperuricemia. Probiotics are powerful weapons to combat metabolic disturbance and intestinal dysbiosis. Previously we isolated a Lactobacillus strain named DM9218 that could reduce the serum uric acid (UA) level by assimilating purine nucleosides. The present study aimed to evaluate the effects of DM9218 on high-fructose-induced hyperuricemia and to elucidate the underlying mechanisms. METHODS: Mice were fed a normal diet, a high-fructose diet, or high-fructose diet with DM9218. Metabolic parameters, fructose- and UA-related metabolites, and fecal microbiota were investigated. Whole-genome sequencing of strain DM9218 was also conducted. In addition, an inosine hydrolase from DM9218 was heterologously expressed in Escherichia coli, and its inosine-degrading activity was detected. RESULTS: Our results indicated that DM9218 could decrease serum UA level and hepatic xanthine oxidase activity in fructose-fed mice. It could protect against high-fructose-induced liver damage and retard UA accumulation by degrading inosine. The modulation effect of DM9218 on high-fructose-induced intestinal dysbiosis resulted in enhancement of intestinal barrier function and reduction of liver lipopolysaccharide, which was closely correlated with the down-regulation of inflammatory cytokine-stimulated xanthine oxidase expression and activity. CONCLUSIONS: Lactobacillus brevis DM9218 is a probiotic strain with the potential to ameliorate fructose-induced hyperuricemia.
OBJECTIVE: High fructose consumption exacerbates purine degradation and intestinal dysbiosis, which are closely related to the development of hyperuricemia. Probiotics are powerful weapons to combat metabolic disturbance and intestinal dysbiosis. Previously we isolated a Lactobacillus strain named DM9218 that could reduce the serum uric acid (UA) level by assimilating purinenucleosides. The present study aimed to evaluate the effects of DM9218 on high-fructose-induced hyperuricemia and to elucidate the underlying mechanisms. METHODS:Mice were fed a normal diet, a high-fructose diet, or high-fructose diet with DM9218. Metabolic parameters, fructose- and UA-related metabolites, and fecal microbiota were investigated. Whole-genome sequencing of strain DM9218 was also conducted. In addition, an inosine hydrolase from DM9218 was heterologously expressed in Escherichia coli, and its inosine-degrading activity was detected. RESULTS: Our results indicated that DM9218 could decrease serum UA level and hepatic xanthine oxidase activity in fructose-fed mice. It could protect against high-fructose-induced liver damage and retard UA accumulation by degrading inosine. The modulation effect of DM9218 on high-fructose-induced intestinal dysbiosis resulted in enhancement of intestinal barrier function and reduction of liver lipopolysaccharide, which was closely correlated with the down-regulation of inflammatory cytokine-stimulated xanthine oxidase expression and activity. CONCLUSIONS:Lactobacillus brevis DM9218 is a probiotic strain with the potential to ameliorate fructose-induced hyperuricemia.
Authors: Ying Wu; Ze Ye; Pengya Feng; Rong Li; Xiao Chen; Xiaozhu Tian; Rong Han; Apurva Kakade; Pu Liu; Xiangkai Li Journal: Gut Microbes Date: 2021 Jan-Dec