Inulin supplementation ameliorates hyperuricemia and modulates gut microbiota in Uox-knockout mice

作者：Yingjie Guo, Yanan Yu, Hailong Li, Xueli Ding, Xiaoyu Li, Xue Jing, Jianwei Chen, Guilin Liu, Yuan Lin, Chen Jiang, Zhen Liu, Yuwei He, Changgui Li, Zibin Tian · 发表于：European Journal of Nutrition · 年份：2020 · DOI：10.1007/s00394-020-02414-x · 被引用次数：208 · 研究领域：Gout, Hyperuricemia, Uric Acid、Gut microbiota and health、Microbial Metabolites in Food Biotechnology

PURPOSE: Inulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to evaluate the role of inulin in hyperuricemia and microbial composition of the gut microbiota in a mouse model of hyperuricemia established through knockout of Uox (urate oxidase) gene. METHODS: KO (Uox-knockout) and WT (wild-type) mice were given inulin or saline by gavage for 7 weeks. The effect of inulin to combat hyperuricemia was determined by assessing the changes in serum UA (uric acid) levels, inflammatory parameters, epithelial barrier integrity, fecal microbiota alterations, and SCFA (short-chain fatty acid) concentrations in KO mice. RESULTS: Inulin supplementation can effectively alleviate hyperuricemia, increase the expressions of ABCG2 in intestine, and downregulate expression and activity of hepatic XOD (xanthine oxidase) in KO mice. It was revealed that the levels of inflammatory cytokines and the LPS (lipopolysaccharide) were remarkably higher in the KO group than those in the WT group, indicating systemic inflammation of hyperuricemic mice, but inulin treatment ameliorated inflammation in KO mice. Besides, inulin treatment repaired the intestinal epithelial barrier as evidenced by increased levels of intestinal TJ (tight junction) proteins [ZO-1 (zonula occludens-1) and occluding] in KO mice. Moreover, serum levels of uremic toxins, including IS (indoxyl sulfate) and PCS (p-cresol sulfate)...