Review

The exposome and health: Where chemistry meets biology

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Science  24 Jan 2020:
Vol. 367, Issue 6476, pp. 392-396
DOI: 10.1126/science.aay3164

Figures

  • Fig. 1 The exposome concept.

    The exposome is an integrated function of exposure on our body, including what we eat and do, our experiences, and where we live and work. The chemical exposome is an important and integral part of the exposome concept. Examples of external stressors are adapted from (39). These stressors are reflected in internal biological perturbations (Fig. 3); therefore, exposures are not restricted to chemicals (toxicants) entering the body, but also include chemicals produced by biological and other natural processes.

  • Fig. 2 Chemical complexity of HRMS and the exposome.

    Top: Known versus unknown features in a typical HRMS measurement [data from (7)]. Bottom: Selected data sources relevant to the chemical exposome (1014, 19). Arrows show the overlap of potential neurotoxicants in FooDB (http://foodb.ca/) and FooDB components in NORMAN SusDat (www.norman-network.com/nds/susdat/) (prioritized chemicals of environmental interest).

  • Fig. 3 Impact of the exposome on subcellular networks.

    (A) Network medicine views the cell as a multilayer network with three principal, interdependent layers: (i) a regulatory network capturing all interactions affecting RNA and protein expression, (ii) a protein interaction network that captures all binding interactions responsible for the formation of protein complexes and signaling, and (iii) a metabolic network representing all metabolic reactions, including those derived from the microbiome, a network of interacting bacteria linked through the exchange of metabolites. Exposome-related factors can affect each layer of this multilayer network. (B) For example, the polyphenol epigallocatechin gallate (EGCG), a biochemical compound in green tea with potential therapeutic effects on type 2 diabetes mellitus (T2D), binds to at least 52 proteins (40). Network-based metrics reveal a proximity between these targets and 83 proteins associated with T2D, suggesting multiple mechanistic pathways to potentially account for the relationship between green tea consumption and reduced risk of T2D. (C) As another example, trichloroethylene (TCE) is a volatile organic compound that was widely used in industrial settings and is now a widespread environmental contaminant present in drinking water, indoor environments, ambient air, groundwater, and soil. Multiple lines of evidence support a link between TCE exposure and kidney cancer and possibly non-Hodgkin’s lymphoma (33). TCE perturbs at least two different layers of the cellular network: It covalently binds to proteins from the protein interaction network, altering their function, and affects the cellular metabolic network, eventually leading to adenosine triphosphate (ATP) depletion. Network-based tools could be used to explore the mechanistic role of many other exposome chemicals on our health and to build experimentally testable hypotheses.

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