Merging the exposome in an integrated framework for "omic" sciences

Abstract To highlight the importance of non-genetic factors in human health, the exposome was introduced as a concept that encouraged holistic consideration of the exposures an individual experiences over their lifetime in the study of diseases. Recognizing the critical role of underlying endogenous processes in the continuum from exposure to disease, practical application of the exposome to human studies often includes in-depth biological characterization across OMIC layers to better understand mechanisms underlying diseases. As a result, the definition of the exposome has evolved to include the importance of considering both exposure and the accumulated biological responses across the lifespan. However, disconnect between the original concept and practical framework has promoted divergent interpretations of the exposome across disciplines and reinforced separation of the environmental (emphasizing exposures) and biological (emphasizing responses) research communities. In particular, whilst knowledge of biological responses can help to distinguish actual (i.e. experienced) from potential exposures and is useful for implementation of the concept, the inclusion of endogenous processes has generated confusion about the position of the exposome in a wider systems biology context. We propose the integration of the exposome within a multi-omics framework by i) reattributing ‘exposome’ to exclusively represent exposures; ii) generalizing the concept to all organisms and ecological levels; iii) aligning terminology across disciplines and iv) introducing ’functional exposomics’ to denote the systematic study of exposure-phenotype interaction. The updates clarify the position of the exposome with respect to other ‘-omics’ and bridge differing perspectives and semantics to facilitate communication between environmental and biological research fields. Harmonization should promote collaborative functional exposomics research efforts, which will be critical to understand the influence of environmental determinants on phenotype and health