Metabolomic changes associated with chronic arsenic exposure in a Bangladeshi population. (April 2023)

• Record Type: Journal Article
• Authors: Wu, Haotian; Kalia, Vrinda; Niedzwiecki, Megan M.; Kioumourtzoglou, Marianthi-Anna; Pierce, Brandon; Ilievski, Vesna; Goldsmith, Jeff; Jones, Dean P.; Navas-Acien, Ana; Walker, Douglas I.; Gamble, Mary V.
• Is Part Of: Chemosphere. Volume 320(2023)
• Publication Date: 2023-04
• Subjects: Arsenic -- Metabolomics -- One carbon metabolism -- TCA cycle -- Folate -- Folic acid; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2023.137998
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Chronic exposure to arsenic (As) remains a global public health concern and our understanding of the biological mechanisms underlying the adverse effects of As exposure remains incomplete. Here, we used a high-resolution metabolomics approach to examine how As affects metabolic pathways in humans. We selected 60 non-smoking adults from the Folic Acid and Creatine Trial (FACT). Inorganic (As III, As V ) and organic (monomethylarsonous acid [MMAs], dimethylarsinous Acid [DMAs]) As species were measured in blood and urine collected at baseline and at 12 weeks. Plasma metabolome profiles were measured using untargeted high-resolution mass spectrometry. Associations of blood and urinary As with 170 confirmed metabolites and >26, 000 untargeted spectral features were modeled using a metabolome-wide association study (MWAS) approach. Models were adjusted for age, sex, visit, and BMI and corrected for false discovery rate (FDR). In the MWAS screening of confirmed metabolites, 17 were associated with ≥1 blood As species (FDR<0.05), including fatty acids, neurotransmitter metabolites, and amino acids. These results were consistent across blood As species and between blood and urine As. Untargeted MWAS identified 423 spectral features associated with ≥1 blood As species. Unlike the confirmed metabolites, untargeted model results were not consistent across As species, with As V and DMAs showing distinct association patterns. Mummichog pathway analysis revealed 12 enriched metabolic pathways that overlapped with the 17 identified metabolites, including one carbon metabolism, tricarboxylic acid cycle, fatty acid metabolism, and purine metabolism. Exposure to As may affect numerous essential pathways that underlie the well-characterized associations of As with multiple chronic diseases. Graphical abstract: Image 1 Highlights: Targeted analyses identified 17 metabolites associated with blood arsenic levels Untargeted screening identified 12 metabolic pathways associated with blood arsenic Altered pathways were consistent with changes to one-carbon metabolomics Most effects were common across all arsenic species Some pathways and associations were unique to arsenate and dimethylarsinous acid Abstract : This trial was registered at https://clinifscaltrials.gov as NCT01050556.