Abnormal metabolism of gut microbiota reveals the possible molecular mechanism of nephropathy induced by hyperuricemia

被引:135
作者
Pan, Libin [1 ]
Han, Pei [1 ]
Ma, Shurong [1 ]
Peng, Ran [1 ]
Wang, Can [1 ]
Kong, Weijia [2 ]
Cong, Lin [1 ]
Fu, Jie [1 ]
Zhang, Zhengwei [1 ]
Yu, Hang [1 ]
Wang, Yan [1 ]
Jiang, Jiandong [1 ]
机构
[1] Chinese Acad Med Sci, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Peking Union Med Coll, Beijing 100050, Peoples R China
[2] Chinese Acad Med Sci, Inst Med Biotechnol, Peking Union Med Coll, Beijing 100050, Peoples R China
基金
中国国家自然科学基金;
关键词
Hyperuricemia; Renal function; Gut microbiota; Metabolomics; Urease; CHRONIC KIDNEY-DISEASE; URIC-ACID; AMINO-ACIDS; RENAL METABOLISM; P-CRESOL; XANTHINE-OXIDASE; IN-VIVO; GLUTAMINE; GLYCINE; SERINE;
D O I
10.1016/j.apsb.2019.10.007
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:249 / 261
页数:13
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