Abnormal metabolism of gut microbiota reveals the possible molecular mechanism of nephropathy induced by hyperuricemia
Abnormal metabolism of gut microbiota reveals the possible molecular mechanism of nephropathy induced by hyperuricemia
复制标题
肠道菌群代谢异常揭示高尿酸血症肾病可能的分子机制
DOI：
10.1016/j.apsb.2019.10.007
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发表时间：
2020-02-01
影响因子：
14.5
通讯作者：
Jiang, Jiandong
中科院分区：
文献类型：
--
作者：
Pan, Libin;Han, Pei;Jiang, Jiandong
高尿酸血症疾病的进展往往伴随着肾功能损害。但关于高尿酸血症肾病的研究很少，特别是其与肠道植物群的关系。本研究结合代谢组学和肠道菌群多样性分析，以大鼠为模型，探讨代谢变化以及肠道植物群组成的变化。结果表明，氨基酸代谢受到干扰，丝氨酸，谷氨酸和谷氨酰胺被下调，而甘氨酸，羟脯氨酸和丙氨酸被上调。甘氨酸、丝氨酸和谷氨酸联合应用可预测高尿酸血症肾病，曲线下面积为1.00。还观察到肠道植物群失衡。模型组中黄杆菌、拟糜杆菌、棒状杆菌、产碱菌、寡杆菌等条件致病菌明显增多，而短链脂肪酸产生菌布劳特氏菌和罗斯拜瑞氏菌则明显减少。在门、科和属的水平上，检测到肠道微生物群中的氮循环紊乱。模型组大鼠尿酸分解途径增强，尿素肝肠循环增强。提示肠道植物群在高尿酸血症肾病的发病中起重要作用。因此，调节肠道微生物群或靶向代谢酶，即，尿素酶，可以帮助治疗和预防这种疾病。(C)2020中国药学会、中国医学科学院药物研究所。制作和主办：Elsevier B.V.
The progression of hyperuricemia disease is often accompanied by damage to renal function. However, there are few studies on hyperuricemia nephropathy, especially its association with intestinal flora. This study combines metabolomics and gut microbiota diversity analysis to explore metabolic changes using a rat model as well as the changes in intestinal flora composition. The results showed that amino acid metabolism was disturbed with serine, glutamate and glutamine being downregulated whilst glycine, hydroxyproline and alanine being upregulated. The combined glycine, serine and glutamate could predict hyperuricemia nephropathy with an area under the curve of 1.00. Imbalanced intestinal flora was also observed. Flavobacterium, Myroides, Corynebacterium, Alcaligenaceae, Oligella and other conditional pathogens increased significantly in the model group, while Blautia and Roseburia, the shortchain fatty acid producing bacteria, declined greatly. At phylum, family and genus levels, disordered nitrogen circulation in gut microbiota was detected. In the model group, the uric acid decomposition pathway was enhanced with reinforced urea liver-intestine circulation. The results implied that the intestinal flora play a vital role in the pathogenesis of hyperuricemia nephropathy. Hence, modulation of gut microbiota or targeting at metabolic enzymes, i.e., urease, could assist the treatment and prevention of this disease. (C) 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.