Deciphering Lipidomics Landscape of Urine Extracellular Vesicles in Alcohol Use Disorder Patients

Urine extracellular vesicles (EVs) have garnered increasing interest in recent years, as their lipid content represents a promising source of noninvasive biomarkers. Alcohol use disorder (AUD) is one of the most common psychiatric disorders and is a major contributor to morbidity and mortality. Accordingly, there is growing interest in assessing prior alcohol consumption and evaluating the severity of liver or brain injury, particularly through noninvasive methods. In this study, we employed a novel approach based on urine EVs and a highly sensitive lipidomics strategy to characterize lipid species in male AUD patients as well as to evaluate the differential functional roles and enzymatic activity networks of urine EV lipids. Our results demonstrate, for the first time, that the lipidomic profiling of urine EVs in male AUD patients is characterized by an enrichment of fatty acyls and glycerophospholipids, with FA 22:0 emerging as a potential biomarker. Notably, increased acyl chain saturation and elevated levels of long-chain fatty acids (22-24 carbons) suggest links to AUD-associated inflammation, cancer, and metabolic dysfunction. These findings advance the understanding of the urine EV lipidome and may contribute to the identification of novel lipid targets and the development of noninvasive biomarkers in AUD.