Urinary Metabolomic Alterations Associated with Contrasting Ambient Air Pollution Exposure in Thai Adults: An...

Ambient fine particulate matter (PM_2.5) is associated with oxidative stress, metabolic dysregulation, and cardiometabolic disease. However, systemic metabolic responses to contrasting real-world ambient air pollution exposure environments remain poorly characterized. In this cross-sectional study, untargeted proton nuclear magnetic resonance (¹H-NMR)-based urinary metabolomics was used to investigate metabolic signatures associated with contrasting ambient air pollution exposure environments in Thailand. Adults residing in Chiang Mai (high-exposure region; n = 51) and Songkhla (low-exposure region; n = 52) were recruited during a period of elevated regional air pollution, with long-term residence serving as a proxy for differential exposure to ambient air pollution environments. Partial least squares-discriminant analysis (PLS-DA) demonstrated separation between exposure groups (R² = 0.873, Q² = 0.447), indicating good model fit but only modest predictive ability. Eight urinary metabolites differed significantly (p < 0.05), implicating pathways related to tryptophan metabolism, nucleotide metabolism, energy metabolism, and host-microbial co-metabolism. L-arginine and L-cystathionine showed lower relative abundance in the high-exposure group, and six metabolites remained significant after Benjamini-Hochberg false discovery rate correction. Following covariate adjustment, L-tryptophan, hippuric acid, xanthine, and 5-hydroxyindoleacetic acid (5-HIAA) remained significantly associated with the high-exposure group. Contrasting ambient air pollution exposure environments, indexed by regional PM_2.5 concentrations, were associated with coordinated urinary metabolic alterations. Because long-term regional residence served as a proxy for individual-level exposure and diet and lifestyle differences between regions were not fully controlled, these findings should be interpreted as associations with contrasting regional exposure environments. Metabolite annotations remain putative and require validation in longitudinal studies with comprehensive pollutant characterization and individual-level exposure assessment.