Utilizing a Biology-Driven Approach to Map the Exposome in Health and Disease: An Essential Investment to Drive the Next Generation of Environmental Discovery

Environ Health Perspect. 2021 Aug;129(8):85001. doi: 10.1289/EHP8327. Epub 2021 Aug 26.


Background: Recent developments in technologies have offered opportunities to measure the exposome with unprecedented accuracy and scale. However, because most investigations have targeted only a few exposures at a time, it is hypothesized that the majority of the environmental determinants of chronic diseases remain unknown.

Objectives: We describe a functional exposome concept and explain how it can leverage existing bioassays and high-resolution mass spectrometry for exploratory study. We discuss how such an approach can address well-known barriers to interpret exposures and present a vision of next-generation exposomics.

Discussion: The exposome is vast. Instead of trying to capture all exposures, we can reduce the complexity by measuring the functional exposome-the totality of the biologically active exposures relevant to disease development-through coupling biochemical receptor-binding assays with affinity purification-mass spectrometry. We claim the idea of capturing exposures with functional biomolecules opens new opportunities to solve critical problems in exposomics, including low-dose detection, unknown annotations, and complex mixtures of exposures. Although novel, biology-based measurement can make use of the existing data processing and bioinformatics pipelines. The functional exposome concept also complements conventional targeted and untargeted approaches for understanding exposure-disease relationships.

Conclusions: Although measurement technology has advanced, critical technological, analytical, and inferential barriers impede the detection of many environmental exposures relevant to chronic-disease etiology. Through biology-driven exposomics, it is possible to simultaneously scale up discovery of these causal environmental factors. https://doi.org/10.1289/EHP8327.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Environmental Exposure / analysis
  • Environmental Health
  • Exposome*
  • Humans
  • Mass Spectrometry