Seasonal PM2.5 Exposure and Plasma Metabolome Changes Related to Metabolic Syndrome in Healthy Adults in Chiang Mai, Thailand

Chiang Mai, Thailand, experiences seasonal fine particulate matter (PM2.5) pollution associated with metabolic diseases, but the underlying mechanisms remain unclear. This prospective observational study compared plasma metabolomes of 25 healthy adults in Samoeng District, a highly affected area, between low and high PM2.5 exposure seasons using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Twenty-six metabolites differentiating haze and non-haze seasons were identified using PLS-DA (VIP > 1.5). During the haze season, 11 were elevated, whereas 15 were decreased. Among the elevated metabolites, the top five—maleylacetoacetic acid, deoxyribose 5-phosphate, betaine, 3-hydroxyanthranilic acid, and 1-methyladenosine—were associated with inflammation, increased reactive oxygen species, nitric oxide inhibition, and altered amino acid metabolism. The top five decreased metabolites—deoxyguanosine, D-arabitol, glycerophosphocholine, ophthalmic acid, and oxaloacetic acid—were involved in several metabolic pathways, particularly those involved in energy metabolism. A total of 56 metabolic pathways were altered by high PM2.5 exposure, including pathways related to amino acids, lipids, sugars, nucleotides, vitamins, and energy metabolism. High PM2.5 exposure disrupts metabolites and pathways, inducing inflammation, oxidative stress, impaired lipid/energy metabolism, insulin resistance, and high blood pressure. These alterations may increase the risk of metabolic and cardiovascular diseases, with dysregulated metabolites serving as potential biomarkers. These findings highlight the molecular impact of air pollution in affected populations and may support preventive strategies and public health policy development in affected regions. Further studies are needed to clarify these findings.