Longitudinal metabolomics of human plasma reveal metabolic dynamics and predictive markers of antituberculosis drug-induced liver injury

• Published in: Respiratory research Vol. 25; no. 1; pp. 254 - 12
• Main Authors: Li, Mengjiao, Zhang, Dan, Yang, Qingxin, Zhao, Zhenzhen, Zhang, Chunying, Zhou, Yanbing, Bai, Yangjuan, Chen, Lu, Tang, Xiaoyan, Liu, Cuihua, Zhou, Juan, Chen, Xuerong, Ying, Binwu
• Format: Journal Article
• Language: English
• Published: London BioMed Central 21.06.2024; BioMed Central Ltd; BMC
• Subjects: Adult; Analysis; Antitubercular Agents - adverse effects; Bile acid metabolism; Bile Acids and Salts - blood; Bile Acids and Salts - metabolism; Biomarker; Biomarkers - blood; Blood plasma; Chemical and Drug Induced Liver Injury - blood; Chemical and Drug Induced Liver Injury - diagnosis; Chemical and Drug Induced Liver Injury - metabolism; Complications and side effects; Development and progression; Drug therapy; Drug-induced liver injury; Fatty acid metabolism; Female; Health aspects; Humans; Liver diseases; Longitudinal Studies; Male; Medicine; Medicine & Public Health; Metabolites; Metabolomics; Metabolomics - methods; Middle Aged; Physiological aspects; Pneumology/Respiratory System; Predictive Value of Tests; Prospective Studies; Tuberculosis; Tuberculosis - blood; Tuberculosis - drug therapy; Tuberculosis - metabolism; China; Metabolomics; Biomarker; Drug-induced liver injury; Tuberculosis
• ISSN: 1465-993X; 1465-9921; 1465-993X
• DOI: 10.1186/s12931-024-02837-8

Tuberculosis (TB) remains the second leading cause of death from a single infectious agent and long-term medication could lead to antituberculosis drug-induced liver injury (ATB-DILI). We established a prospective longitudinal cohort of ATB-DILI with multiple timepoint blood sampling and used untargeted metabolomics to analyze the metabolic profiles of 107 plasma samples from healthy controls and newly diagnosed TB patients who either developed ATB-DILI within 2 months of anti-TB treatment (ATB-DILI subjects) or completed their treatment without any adverse drug reaction (ATB-Ctrl subjects). The untargeted metabolome revealed that 77 metabolites (of 895 total) were significantly changed with ATB-DILI progression. Among them, levels of multiple fatty acids and bile acids significantly increased over time in ATB-DILI subjects. Meanwhile, metabolites of the same class were highly correlated with each other and pathway analysis indicated both fatty acids metabolism and bile acids metabolism were up-regulated with ATB-DILI progression. The targeted metabolome further validated that 5 fatty acids had prediction capability at the early stage of the disease and 6 bile acids had a better diagnostic performance when ATB-DILI occurred. These findings provide evidence indicating that fatty acids metabolism and bile acids metabolism play a vital role during ATB-DILI progression. Our report adds a dynamic perspective better to understand the pathological process of ATB-DILI in clinical settings.