Alteration of Bile Acids and Omega-6 PUFAs Are Correlated With the Progression and Prognosis of Drug-Induced Liver Injury

作者：Shuang Zhao, Haoshuang Fu, Tianhui Zhou, Minghao Cai, Yan Huang, Qinyi Gan, Chenxi Zhang, Cong Qian, Jiexiao Wang, Zhenglan Zhang, Xiaolin Wang, Xiaogang Xiang, Qing Xie · 发表于：Frontiers in Immunology · 年份：2022 · DOI：10.3389/fimmu.2022.772368 · 被引用次数：25 · 研究领域：Drug-Induced Hepatotoxicity and Protection、Liver Disease Diagnosis and Treatment、Liver physiology and pathology

Background & Aims: Drug-induced liver injury (DILI) is one of the leading causes of liver failure with some of the patients progressed to chronic DILI. The mechanisms underlying the severity and chronicity of DILI are poorly elucidated and the biomarkers are limited. Metabolites and gut microbiota played a crucial role in the development of various liver diseases. Herein, a systematic analysis of serum metabolites and gut microbiota was performed in DILI patients, aiming to identify metabolites correlated with the progression and clinical prognosis of DILI. Methods: Various serum metabolites were quantitated using a metabolite array technology in this prospective study. Gut microbiome compositions and the expression profiles of liver genes were determined in patients with DILI and healthy controls. Results: Metabolomic analysis revealed that bile acids (BAs) and polyunsaturated fatty acids (PUFAs) were closely related to DILI severity and chronicity respectively. The ratios of serum primary/secondary BAs and omega-6/omega-3 PUFAs were elevated in DILI patients. A model established by adrenic acid (AdA) and aspartic acid (Asp) exerts good performance for predicting the chronicity of DLIL. Hepatic transcriptome revealed enhanced expression of PUFA peroxidation and supressed expression of BA synthesis related genes in DILI patients. In addition, Lactic acid bacteria and BA converting bacteria were increased in gut of DILI patients. Besides, elevated serum malondialdehyde (MDA) a...