Characterization of the Human Exposome by a Comprehensive and Quantitative Large-Scale Multianalyte Metabolomics Platform

The
exposome, defined as the cumulative measure of external exposures
and associated biological responses throughout the lifespan, has emerged
in recent years as a cornerstone in biomedical sciences. Metabolomics
stands out here as one of the most powerful tools for investigating
the interplay between the genetic background, exogenous, and endogenous
factors within human health. However, to address the complexity of
the exposome, novel methods are needed to characterize the human metabolome.
In this work, we have optimized and validated a multianalyte metabolomics
platform for large-scale quantitative exposome research in plasma
and urine samples, based on the use of simple extraction methods and
high-throughput metabolomic fingerprinting. The methodology enables,
for the first time, the simultaneous characterization of the endogenous
metabolome, food-related metabolites, pharmaceuticals, household chemicals,
environmental pollutants, and microbiota derivatives, comprising more
than 1000 metabolites in total. This comprehensive and quantitative
investigation of the exposome is achieved in short run times, through
simple extraction methods requiring small-sample volumes, and using
integrated quality control procedures for ensuring data quality. This
metabolomics approach was satisfactorily validated in terms of linearity,
recovery, matrix effects, specificity, limits of quantification, intraday
and interday precision, and carryover. Furthermore, the clinical potential
of the methodology was demonstrated in a dietary intervention trial
as a case study. In summary, this study describes the optimization,
validation, and application of a multimetabolite platform for comprehensive
and quantitative metabolomics-based exposome research with great utility
in large-scale epidemiological studies.