Untargeted Plasma Metabolomics Reveals Metabolic Differences Associated with Job Stress in Manufacturing Workers: A Cross-Sectional Study

Background: Job stress is a common occupational hazard and has been linked to adverse mental and cardiometabolic outcomes; however, the metabolic responses to job stress remain incompletely understood. This study aimed to characterize plasma metabolic alterations associated with job stress and identify the potential metabolic pathways involved. Methods: A total of 195 male manufacturing workers aged 20–60 years were recruited in Fuzhou, China. After applying the inclusion and exclusion criteria and screening for outliers, 143 participants were included in the final analysis, comprising 78 workers in the job stress group and 65 in the non-job stress group. Job stress was assessed using the revised Chinese Job Content Questionnaire on the basis of the demand–control model, with a demand-to-control ratio > 1.0 warranting inclusion in the stress group. Fasting plasma samples were analyzed through untargeted liquid chromatography–mass spectrometry (LC–MS). Differentially abundant metabolites were identified using univariate and multivariate statistical approaches, and pathway enrichment analyses were conducted using MetaboAnalyst 6.0. Results: Twelve plasma metabolite features, predominantly lipid species such as phosphatidylethanolamine (PE), diacylglycerol (DG), and free fatty acids, were significantly associated with job stress after adjustment for covariates. Five features (M573T1, M264T3, M673T5, M686T27 and M569T1) showed moderate discriminative ability (AUC > 0.7) for job stress exposure. Pathway analysis revealed enrichment of seven metabolic pathways, among which glycerophospholipid metabolism was significantly enriched (FDR_P < 0.05). Conclusions: Untargeted plasma metabolomics revealed distinct metabolic differences associated with job stress, particularly in relation to lipid metabolism and membrane remodeling pathways. These findings provide preliminary evidence supporting the utility of metabolomics in exploring occupational stress-related metabolic signatures and identifying exploratory candidate markers for further validation.