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短乳杆菌 DM9218 通过降解肌苷和调节肠道菌群失调来改善果糖诱导的高尿酸血症。

Lactobacillus brevis DM9218 ameliorates fructose-induced hyperuricemia through inosine degradation and manipulation of intestinal dysbiosis.

机构信息

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.

Department of Gastroenterology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Nutrition. 2019 Jun;62:63-73. doi: 10.1016/j.nut.2018.11.018. Epub 2018 Nov 26.

DOI:10.1016/j.nut.2018.11.018
PMID:30852460
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.

摘要

目的

高果糖的摄入会加剧嘌呤降解和肠道菌群失调,而这两者与高尿酸血症的发展密切相关。益生菌是对抗代谢紊乱和肠道菌群失调的有力武器。此前,我们分离到一株名为 DM9218 的乳杆菌,它可以通过同化嘌呤核苷来降低血清尿酸(UA)水平。本研究旨在评估 DM9218 对高果糖诱导的高尿酸血症的影响,并阐明其潜在机制。

方法

用正常饮食、高果糖饮食或高果糖饮食加 DM9218 喂养小鼠。检测代谢参数、果糖和 UA 相关代谢物以及粪便微生物群。还对菌株 DM9218 进行了全基因组测序。此外,在大肠杆菌中异源表达了 DM9218 中的肌苷水解酶,并检测了其肌苷降解活性。

结果

结果表明,DM9218 可降低果糖喂养小鼠的血清 UA 水平和肝黄嘌呤氧化酶活性。它可以通过降解肌苷来保护果糖诱导的肝损伤和延缓 UA 积累。DM9218 对高果糖诱导的肠道菌群失调的调节作用导致肠道屏障功能增强和肝脏内脂多糖减少,这与炎症细胞因子刺激的黄嘌呤氧化酶表达和活性下调密切相关。

结论

短乳杆菌 DM9218 是一种具有改善果糖诱导的高尿酸血症潜力的益生菌菌株。

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