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

人类血浆代谢组学分析表明,三甲胺 N-氧化物的产生减少可延缓慢性肾病的进展

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

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

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

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 α-smooth muscle actin. In mice, a TMAO-containing diet decreased kidney mass and increased protein expression of α-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.

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