Original articles
Libin Pan, Pei Han, Shurong Ma, Ran Peng, Can Wang, Weijia Kong, Lin Cong, Jie Fu, Zhengwei Zhang, Hang Yu, Yan Wang, Jiandong Jiang. Abnormal metabolism of gut microbiota reveals the possible molecular mechanism of nephropathy induced by hyperuricemia[J]. Acta Pharmaceutica Sinica B, 2020, 10(2): 249-261

Abnormal metabolism of gut microbiota reveals the possible molecular mechanism of nephropathy induced by hyperuricemia
Libin Pana, Pei Hana, Shurong Maa, Ran Penga, Can Wanga, Weijia Kongb, Lin Conga, Jie Fua, Zhengwei Zhanga, Hang Yua, Yan Wanga, Jiandong Jianga
a State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100050, China;
b Insitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100050, China
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.
Key words:    Hyperuricemia    Renal function    Gut microbiota    Metabolomics    Urease   
Received: 2019-07-11     Revised: 2019-10-05
DOI: 10.1016/j.apsb.2019.10.007
Funds: The project was supported by the National Natural Science Foundation of China (Nos. 81573493 and 81973290), CAMS Innovation Fund for Medical Sciences (CIFMS, No. 2016-I2M-3-011, China), Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PDstudy(Z141102004414062,China), the National Megaprojectfor Innovative Drugs (Nos. 2018ZX09711001-002-002 and 2018ZX09302015, China), and Beijing Natural Sciences Fund Key Projects (NO. 7181007). We also thank Shimadzu (China) Co., Ltd. for the technological supports in this study.
Corresponding author: Yan Wang, Jiandong Jiang     Email:wangyan@imm.ac.cn;jiang.jdong@163.com
Author description:
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Libin Pan
Pei Han
Shurong Ma
Ran Peng
Can Wang
Weijia Kong
Lin Cong
Jie Fu
Zhengwei Zhang
Hang Yu
Yan Wang
Jiandong Jiang

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