Longitudinal Exposomics in a Multiomic Wellness Cohort Reveals Distinctive and Dynamic Environmental Chemical Mixtures in Blood

Chemical exposomes
can now be comprehensively measured
in human
blood, but knowledge of their variability and longitudinal stability
is required for robust application in cohort studies. Here, we applied
high-resolution chemical exposomics to plasma of 46 adults, each sampled
6 times over 2 years in a multiomic cohort, resulting in 276 individual
exposomes. In addition to quantitative analysis of 83 priority target
analytes, we discovered and semiquantified substances that have rarely
or never been reported in humans, including personal care products,
pesticide transformation products, and polymer additives. Hierarchical
cluster analysis for 519 confidently annotated substances revealed
unique and distinctive coexposures, including clustered pesticides,
poly(ethylene glycols), chlorinated phenols, or natural substances
from tea and coffee; interactive heatmaps were publicly deposited
to support open exploration of the complex (meta)data. Intraclass
correlation coefficients (ICC) for all annotated substances demonstrated
the relatively low stability of the exposome compared to that of proteome,
microbiome, and endogenous small molecules. Implications are that
the chemical exposome must be measured more frequently than other
omics in longitudinal studies and four longitudinal exposure types
are defined that can be considered in study design. In this small
cohort, mixed-effect models nevertheless revealed significant associations
between testosterone and perfluoroalkyl substances, demonstrating
great potential for longitudinal exposomics in precision health research.