Use of High-Resolution Metabolomics to Identify Potential Metabolic Pathways Associated with Traffic-Related Air Pollutants

摘要

Background. High-resolution metabolomics (HRM) has emerged as a promising analytical platform for measuring environmental exposures and corresponding biological response. Questions remain, however, whether HRM can as a sensitive tool for biomarker discovery, especially over short exposure durations. Methods. We conducted HRM to identify potential metabolic pathways and internal biomarkers associated with primary traffic emissions within the Dorm Room Inhalation to Vehicle Emission (DRIVE) study. We measured a suite of air pollutants at multiple ambient and indoor sites along a major highway artery over 12 weeks. In parallel, 54 students living in dormitories either near (20 m) or far (1.4 km) from the highway underwent personal sampling and contributed plasma and saliva. We conducted untargeted HRM on all samples, followed by a Metabolome-Wide Association Study (MWAS), pathway analyses and tandem mass spectrometry (MS/MS). Results. In total, over 20K metabolite features were reliably extracted from plasma, and over 29K from saliva. Over 1300 features were significantly associated with at least one or more traffic pollutant (e.g., black carbon, carbon monoxide, nitrogen oxides (p<0.05), when controlling for covariates and false discovery rate. Pathway analysis indicated elicitation of several inflammatory pathways, including leukotriene metabolism and vitamin E metabolism. We validated 10 metabolites associated with traffic pollutants using MS/MS, including hypoxanthine, g-linolenic acid, L-Histidine, L-Proline, and L-Arginine. Conclusions. We successfully identified and verified several pathways and metabolites using HRM, most consisting of endogenous metabolic signals related to oxidative stress, inflammatory response and nucleic acid damage and repair. These findings offer promising initial evidence of the potential of this analytic platform as a tool for biomarker discovery to ubiquitous environmental stressors.