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.