Dysregulated metabolites serve as novel biomarkers for metabolic diseases caused by e-cigarette vaping and cigarette smoking

Metabolites are essential intermediate products in metabolism, and metabolism dysregu-lation indicates different types of diseases. Previous studies have shown that cigarette smoke dysregulated metabolites; however, limited information is available with electronic cigarette (e-cig) vaping. We hypothesized that e-cig vaping and cigarette smoking alters systemic metabolites, and we propose to understand the specific metabolic signature between e-cig users and cigarette smok-ers. Plasma from non-smoker controls, cigarette smokers, and e-cig users was collected, and metabolites were identified by UPLC–MS (ultra-performance liquid chromatography mass spectrometer). Nicotine degradation was activated by e-cig vaping and cigarette smoking with increased concentrations of cotinine, cotinine N-oxide, (S)-nicotine, and (R)-6-hydroxynicotine. Additionally, we found significantly decreased concentrations in metabolites associated with tricarboxylic acid (TCA) cycle pathways in e-cig users versus cigarette smokers, such as D-glucose, (2R,3S)-2,3-dime-thylmalate, (R)-2-hydroxyglutarate, O-phosphoethanolamine, malathion, D-threo-isocitrate, malic acid, and 4-acetamidobutanoic acid. Cigarette smoking significant upregulated sphingolipid me-tabolites, such as D-sphingosine, ceramide, N-(octadecanoyl)-sphing-4-enine, N-(9Z-octadecenoyl)-sphing-4-enine, and N-[(13Z)-docosenoyl]-sphingosine, versus e-cig vaping. Overall, e-cig vaping dysregulated TCA cycle-related metabolites while cigarette smoking altered sphingolipid metabo-lites. Both e-cig and cigarette smoke increased nicotinic metabolites. Therefore, specific metabolic signatures altered by e-cig vaping and cigarette smoking could serve as potential systemic bi-omarkers for early pathogenesis of cardiopulmonary diseases.