High-Resolution Metabolomic Assessment of Pesticide Exposure in Central Valley, California

Abstract

Pesticides are widely used in the agricultural Central Valley region of California. Historically, this has included organophosphates (OPs), organochlorines (OCs), and pyrethroids (PYRs). This study aimed to identify perturbations of the serum metabolome in response to each class of pesticide and mutual associations between groups of metabolites and multiple pesticides. We conducted high-resolution metabolomic profiling of serum samples from 176 older adults living in the California Central Valley using liquid chromatography with high-resolution mass spectrometry. We estimated chronic pesticide exposure (from 1974 to year of blood draw) to OPs, OCs, and PYRs from ambient sources at homes and workplaces with a geographic information system (GIS)-based model. Based on partial least-squares regression and pathway enrichment analysis, we identified metabolites and metabolic pathways associated with one or multiple pesticide classes, including mitochondrial energy metabolism, fatty acid and lipid metabolism, and amino acid metabolism. Utilizing an integrative network approach, we found that the fatty acid β-oxidation pathway is a common pathway shared across all three pesticide classes. The disruptions of the serum metabolome suggested that chronic pesticide exposure might result in oxidative stress, inflammatory reactions, and mitochondrial dysfunction, all of which have been previously implicated in a wide variety of diseases. Overall, our findings provided a comprehensive view of the molecular mechanisms of chronic pesticide toxicity, and, for the first time, our approach informs exposome research by moving from macrolevel population exposures to microlevel biologic responses.

Cross-species metabolomic analysis of tau- and DDT-related toxicity

“…Comparison of metabolites associated with DDT and its metabolites in worms and human plasma and CSF revealed similar changes in amino acids and metabolites of the inflammatory pathways ( Table S2, Supplementary Material ). The overlapping metabolic pathways indicate changes in drug metabolism pathways, as expected, and additionally, changes in metabolism of precursors of neurotransmitters, butanoate metabolism, and pyrimidine metabolism, which have been previously reported to be associated with exposure to DDT metabolites and organochlorine pesticides ( 125 , 126 ). The concordance between the species further strengthens the use of C. elegans as a model relevant to studying the metabolic effect of exposure to toxicants on human health.…”

Pesticides Exposure-Induced Changes in Brain Metabolome: Implications in the Pathogenesis of Neurodegenerative Disorders

“…The rise in the proportion of the aging population has led to an increase in age-related neurodegenerative disorders. Various metabolic pathways like fatty acid β-oxidation pathway, oxidative stress, mitochondrial dysfunction, glycerophospholipid metabolism, tryptophan metabolism, and glutathione metabolism have been shown to play a role in neurodegenerative diseases (Widner et al 2002;Jenner 2003;Smeyne and Smeyne 2013;Bose and Beal 2016;Yan et al 2021). The causative factors contributing to the onset and development of complex and multigenic neurodegenerative diseases have been attributed to genetic and environmental factors (Brown et al 2005;Cannon and Greenamyre 2013;Pihlstrøm et al 2017).…”

“…Pesticides disrupt critical cellular mechanisms that sustain the metabolic requirements and activity of the nervous system (Keifer and Fireston 2007). Studies speculate that most Alzheimer's disease (AD) and Parkinson's disease (PD) cases observed in the older population might have been exposed to pesticides long before diagnosis (de Pedro-Cuesta et al 2015;Yan et al 2021). Furthermore, Freire and Koifman (2012) reviewed several published prospective and case-control studies and found evidence of an association between pesticide exposure and PD (Freire and Koifman 2012).…”

“…However, metabolomics does not reveal the cause of the disease but shows the final results of normal or altered metabolic functions. Metabolomic assessment of exposure to different classes of pesticides such as organophosphates (OPs), organochlorines (OCs), and pyrethroids (PYRs) in biofluids has shown alteration in metabolites related to oxidative stress, inflammatory reactions, and mitochondrial dysfunction (Yan et al 2021). Furthermore, it has been noted that many of the metabolic pathways altered by pesticides are common to neurodegeneration (Kori et al 2016;Yan et al 2021).…”

“…Metabolomic assessment of exposure to different classes of pesticides such as organophosphates (OPs), organochlorines (OCs), and pyrethroids (PYRs) in biofluids has shown alteration in metabolites related to oxidative stress, inflammatory reactions, and mitochondrial dysfunction (Yan et al 2021). Furthermore, it has been noted that many of the metabolic pathways altered by pesticides are common to neurodegeneration (Kori et al 2016;Yan et al 2021). So, metabolomics can detect metabolite level deviation and identify the affected metabolic pathways, which helps determine the etiology of a neurodegenerative disorder (Jové et al 2014).…”