Metabolomics analysis of human plasma reveals decreased production of trimethylamine N-oxide retards the progression of chronic kidney disease

作者全名："Hu, Da-Yong; Wu, Ming-Yu; Chen, Guang-Qi; Deng, Bing-Qing; Yu, Hai-Bo; Huang, Jian; Luo, Ying; Li, Meng-Yuan; Zhao, Da-Ke; Liu, Jun-Yan"

作者地址："[Hu, Da-Yong; Wu, Ming-Yu; Chen, Guang-Qi; Deng, Bing-Qing; Yu, Hai-Bo; Huang, Jian; Luo, Ying; Li, Meng-Yuan; Zhao, Da-Ke; Liu, Jun-Yan] Shanghai Tenth Peoples Hosp, Div Nephrol & Rheumatol, Shanghai, Peoples R China; [Hu, Da-Yong; Wu, Ming-Yu; Chen, Guang-Qi; Deng, Bing-Qing; Yu, Hai-Bo; Huang, Jian; Luo, Ying; Li, Meng-Yuan; Zhao, Da-Ke; Liu, Jun-Yan] Tongji Univ, Ctr Nephrol & Metabol, Sch Med, Shanghai, Peoples R China; [Liu, Jun-Yan] Chongqing Med Univ, Ctr Novel Target & Therapeut Intervent, Inst Life Sci, Chongqing, Peoples R China"

通信作者："Hu, DY (通讯作者)，Tongji Univ, Ctr Nephrol & Metabol, Sch Med, Shanghai, Peoples R China.; Liu, JY (通讯作者)，Chongqing Med Univ, Ctr Novel Target & Therapeut Intervent, Inst Life Sci, Chongqing, Peoples R China."

来源：BRITISH JOURNAL OF PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000791446500001

JCR分区：Q1

影响因子：7.3

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：chronic kidney disease; cross-sectional study; gut microbiota; metabolomics; renal fibrosis; trimethylamine N-oxide

摘要："Background and Purpose Chronic kidney disease (CKD) is a global public health problem and one of the leading causes of all-cause mortality. However, the pathogenic mechanisms and intervention methods for CKD progression are not fully understood. Experimental Approach Plasma from patients with uraemia and from healthy controls (n = 30 per group) was analysed with LC-MS/MS-based non-targeted metabolomics to identify potential markers of uraemia. These potential markers were validated in the same cohort and a second cohort (n = 195) by quantitative analysis of the markers, using LC-MS/MS. The most promising marker was identified by correlation analysis and further validated using HK-2 cells and mouse models. Key Results Trimethylamine N-oxide (TMAO) was identified as a promising marker among the 18 potential markers found in the first cohort, and it was optimally correlated with renal function of CKD patients in the second cohort. Treatment of HK-2 cells with TMAO decreased cell viability and up-regulated expression of alpha-smooth muscle actin. In mice, a TMAO-containing diet decreased kidney mass and increased protein expression of alpha-smooth muscle actin. Also, control of TMAO production by inhibiting its biosynthetic pathway with 3,3-dimethyl-1-butanol or disrupting gut microbiota function with an antibiotic cocktail, attenuated renal injury in a murine model of CKD. Conclusion and Implications Our data show that decreased TMAO production could be a new strategy to attenuate the progression of renal injury in CKD."

基金机构："National Natural Science Foundation of China [81972709, 81470588, 81970635]"

基金资助正文："National Natural Science Foundation of China, Grant/Award Numbers: 81972709, 81470588, 81970635"