The metabolome: A key measure for exposome research in epidemiology

Abstract

Purpose of review: Application of omics to study human health has created a new era of opportunities for epidemiology research. However, approaches to characterize exogenous health triggers have largely not leveraged advances in analytical platforms and big data. In this review, we highlight the exposome, which is defined as the cumulative measure of exposure and biological responses across a lifetime as a cornerstone for new epidemiology approaches to study complex and preventable human diseases.

Recent findings: While no universal approach exists to measure the entirety of the exposome, use of high-resolution mass spectrometry methods provide distinct advantages over traditional biomonitoring and have provided key advances necessary for exposome research. Application to different study designs and recommendations for combining exposome data with novel data analytic frameworks to study complex interactions of multiple stressors are also discussed.

Summary: Even though challenges still need to be addressed, advances in methods to characterize the exposome provide exciting new opportunities for epidemiology to support fundamental discoveries to improve public health.

Keywords: Environmental epidemiology; Exposome; High-resolution exposomics; High-resolution metabolomics; Metabolome-wide association study; Precision medicine.

Conflict of interest statement

Compliance with Ethical Standards Conflict of Interest Douglas I. Walker, Damaskini Valvi, Nathaniel Rothman, Qing Lan and Dean P. Jones each declare no potential conflicts of interest. Gary W. Miller serves as Editor in Chief of the journal Toxicological Sciences and does receive renumeration for this, but it does not present a conflict.

Figures

Figure 1:

Framework for the metabolome as a central measure for linking exposure to internal dose, biological response and disease. Environmental chemicals absorbed by a host, which are detected within the metabolome in either the parent form or as transformation products represent a measure of exposure internal dose and the exposome contribution to metabolic phenotype. These compounds can influence biological processes through local and global changes within an organism, resulting in micro- and macroscale interactions between environmental chemicals and endogenous processes encoded by the genome, the functional measures of these interactions can be detected as alterations to metabolic processes. By detecting metabolites from most metabolic pathways, metabolomic techniques allow evaluation of these biological changes, which represent markers of effective dose and response. Long-term shifts in metabolic processes accompany disease pathobiology and often represent distinct metabolic phenotypes from controls. Thus, the human metabolome can be used to assess the presence of an exposure and also to provide a framework for study of exposure-response and disease relationships. (Reprinted from Elsevier Books, Douglas I. Walker, Young-Mi Go, Ken Liu, Kurt D. Pennell, Dean P. Jones; Metabolic Phenotyping in Personalized and Public Healthcare, Pages 167–211; Jan 1, 2016; with permission from Elsevier) [111].