Drug-Induced Alterations of Mouse Aorta Lipidome and Their Potential Correlations with the Gut Ecosystem

Drug-induced cardiovascular risk is one of the primary concerns in drug development and clinical practice. Meanwhile, drugs can also alter the gut microbiome, the disturbance of which is correlated with cardiovascular diseases. However, the detailed molecular information underlying these associations is still unclear. Here, we comprehensively investigated the impact of 33 commonly used drugs on the mouse aorta lipidome and gut metaproteome, revealing that 6 out of 8 (75.0%) anticancer drugs and 2 out of 16 (12.5%) cardiovascular drugs significantly altered the aorta lipids, with the majority being downregulated. Drugs triggered a greater increase in phosphatidylethanolamine (PE) with longer fatty acyl chains and higher degrees of unsaturation rather than hydrophobicity. Drugs also tend to suppress gut microbial producers of short-chain fatty acids. Antibiotic pretreatment and conventional mouse models revealed potential drug-host-microbe interactions on the gut-vascular axis. This study provides a deeper insight into the pharmacological actions of the studied drugs with a molecular basis for the management of cancer treatment-related cardiovascular diseases.