Defining the Scope of Exposome Studies and Research Needs from a Multidisciplinary Perspective

Abstract

The concept of the exposome was introduced over 15 years ago to reflect the important role that the environment exerts on health and disease. While originally viewed as a call-to-arms to develop more comprehensive exposure assessment methods applicable at the individual level and throughout the life course, the scope of the exposome has now expanded to include the associated biological response. In order to explore these concepts, a workshop was hosted by the Gunma University Initiative for Advanced Research (GIAR, Japan) to discuss the scope of exposomics from an international and multidisciplinary perspective. This Global Perspective is a summary of the discussions with emphasis on (1) top-down, bottom-up, and functional approaches to exposomics, (2) the need for integration and standardization of LC- and GC-based high-resolution mass spectrometry methods for untargeted exposome analyses, (3) the design of an exposomics study, (4) the requirement for open science workflows including mass spectral libraries and public databases, (5) the necessity for large investments in mass spectrometry infrastructure in order to sequence the exposome, and (6) the role of the exposome in precision medicine and nutrition to create personalized environmental exposure profiles. Recommendations are made on key issues to encourage continued advancement and cooperation in exposomics.

Figure 1

Functional exposomics approach to study the exposome. In the top-down approach, molecular epidemiology studies focus on exposure (e.g., small molecule biomarkers of exogenous compounds, protein adducts, reactive metabolites) and biological response profiles (e.g., metabolomics, gene expression, methylation) within the host using biospecimens. This approach can generate hypotheses regarding exposure–disease and exposure–response relationships but does not necessarily capture direct measures of exposure. In the bottom-up approach, comprehensive data on environmental exposures are collected through surveys, sensors, or trace analytical chemistry in environmental samples (external exposures) or in biospecimens. This can generate hypotheses on effects but does not necessarily investigate the effect. We propose that a functional exposomics study bridges these two approaches and consists of the biologically active exposures present in an individual and specifically examines associations between environmental exposure and biological effect.

Figure 2

Full coverage of the chemical exposome will require multiple instrumental approaches, as shown by the chemical space of 299 internal exogenous analytes routinely targeted in large population biomonitoring studies in blood or urine. a) Measurement of the analytes will require a mixture of LC- and GC-based approaches that are b) dependent upon the analyte class. Analytes were selected from the National Health and Nutrition Examination Survey (1999–2016, latest update in 2019), Centers for Disease Control and Prevention (USA), and HBM4 EU (European Environment Agency, and European Commission, latest update in 2018). Water solubility and K_ow values are estimated from EPA EPI Suite software and span 18 orders of magnitude for water solubility and 15 orders of magnitude for K_ow. Estimations of the K_ow values for the anionic perfluoroalkyl acids included in the class of perfluoroalkyl and polyfluoroalkyl substances are from Hidalgo and Mora-Diez.