Particulate metal exposures induce plasma metabolome changes in a commuter panel study

• Type of Material: Article
• Authors: Chandresh Nanji Ladva, Emory University; Rachel Golan, Ben Gurion University of the Negev; Donghai Liang, Emory University; Roby Greenwald, Georgia State University; Douglas Walker, Emory University; Karan Uppal, Emory University; Amit U. Raysoni, Emory University; ViLinh Tran, Emory University; Tianwei Yu, Emory University; W Dana Flanders, Emory University; Gary Miller, Emory University; Dean Jones, Emory University; Jeremy Sarnat, Emory University
• Language: English
• Date: 2018-09-19
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2018 Ladva et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0203468
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 13
• Issue: 9
• Start Page: e0203468
• End Page: e0203468
• Grant/Funding Information: RG gratefully acknowledges support by a post-doctoral fellowship from the Environment and Health Fund, Jerusalem, Israel.; The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the USEPA. Further, USEPA does not endorse the purchase of any commercial products or services mentioned in the publication.; The presented research was supported by a Clean Air Research Center grant to Emory University and the Georgia Institute of Technology from the US Environmental Protection Agency (USEPA, RD834799) and the Human Exposome Research Center (HERCULES) (NIH, P30 ES019776).; Shared instrumentation for metabolomics analysis was supported through the National Institutes of Health (NIH, OD018006). CL acknowledges pre-doctoral support from a training grant (NIH, T32 ES012870-13) and the Burroughs Wellcome Fund through the Molecules the Mankind Doctoral Pathway at Emory University.
• Keywords: MATTER; Science & Technology - Other Topics; Science & Technology; Multidisciplinary Sciences; ASSOCIATION; INFLAMMATION; OXIDATIVE STRESS; C-REACTIVE PROTEIN; AIR-POLLUTION; HIGH-RESOLUTION METABOLOMICS; ASTHMA CONTROL; CAR COMMUTERS; BLOOD
• Research Categories: Health Sciences, Epidemiology; Biology, Biostatistics; Health Sciences, Public Health

Abstract

Introduction Advances in liquid chromatography-mass spectrometry (LC-MS) have enabled high-resolution metabolomics (HRM) to emerge as a sensitive tool for measuring environmental exposures and corresponding biological response. Using measurements collected as part of a large, panel-based study of car commuters, the current analysis examines in-vehicle air pollution concentrations, targeted inflammatory biomarker levels, and metabolomic profiles to trace potential metabolic perturbations associated with on-road traffic exposures. Methods A 60-person panel of adults participated in a crossover study, where each participant conducted a highway commute and randomized to either a side-street commute or clinic exposure session. In addition to in-vehicle exposure characterizations, participants contributed pre- and post-exposure dried blood spots for 2-hr changes in targeted proinflammatory and vascular injury biomarkers and 10-hr changes in the plasma metabolome. Samples were analyzed on a Thermo QExactive MS system in positive and negative electrospray ionization (ESI) mode. Data were processed and analyzed in R using apLCMS, xMSanalyzer, and limma. Features associated with environmental exposures or biological endpoints were identified with a linear mixed effects model and annotated through human metabolic pathway analysis in mummichog. Results HRM detected 10-hr perturbations in 110 features associated with in-vehicle, particulate metal exposures (Al, Pb, and Fe) which reflect changes in arachidonic acid, leukotriene, and tryptophan metabolism. Two-hour changes in proinflammatory biomarkers hs-CRP, IL-6, IL-8, and IL-1β were also associated with 10-hr changes in the plasma metabolome, suggesting diverse amino acid, leukotriene, and antioxidant metabolism effects. A putatively identified metabolite, 20-OH-LTB4, decreased after in-vehicle exposure to particulate metals, suggesting a subclinical immune response. Conclusions Acute exposures to traffic-related air pollutants are associated with broad inflammatory response, including several traditional markers of inflammation.