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 robust application of chemical exposomics in cohort studies requires knowledge of the longitudinal stability and interindividual variability of exogenous molecular profiles. Here we applied chemical exposomics to plasma of 46 adults, each sampled six times over two years in a multiomic wellness cohort. New chemicals were discovered, distinctive co-exposure patterns were observed, and intra-class correlation coefficients (ICC) for 519 confidently annotated substances are reported to support study design. Longitudinal stability of the chemical exposome (mean ICC 0.30) was significantly lower than the proteome, metabolome, lipidome or microbiome, and must be measured more frequently than other molecular profiles in health studies. Mixed-effects models nevertheless revealed significant associations between testosterone and perfluoroalkyl substances, and significant time-trends for low and high stability exposures alike. Complex exposome data structures were visualized and explored, demonstrating great potential for longitudinal exposomics in precision health research.