Tackling the Complexity of the Exposome: Considerations from the Gunma University Initiative for Advanced Research (GIAR) Exposome Symposium

Abstract

The attempt to describe complex diseases by solely genetic determination has not been successful. There is increasing recognition that the development of disease is often a consequence of interactions between multiple genetic and environmental factors. To date, much of the research on environmental determinants of disease has focused on single exposures generally measured at a single time point. In order to address this limitation, the concept of the exposome has been introduced as a comprehensive approach, studying the full complement of environmental exposures from conception onwards. However, exposures are vast, dynamic, and diverse, and only a small proportion can be reasonably measured due to limitations in technology and feasibility. In addition, the interplay between genes and exposure as well as between different exposures is complicated and multifaceted, which leads to difficulties in linking disease or health outcomes with exposures. The large numbers of collected samples require well-designed logistics. Furthermore, the immense data sets generated from exposome studies require a significant computational investment for both data analysis and data storage. This report summarizes discussions during an international exposome symposium held at Gunma University in Japan regarding the concept of the exposome, challenges in exposome research, and future perspectives in the field.

Exposomal research in the context of birth cohorts

“…46 Biological samples, including blood, hair, urine, and breast milk, are widely used in birth cohort studies to evaluate contamination exposures, such as organochlorine and brominated compounds, perfluoroalkyl substances and metals, phthalate metabolites, phenols, organophosphate pesticide metabolites, and cotinine. 24,47 An exciting and evolving aspect of exposomal research is the development of omics technologies.…”

Environmental DNA and RNA as Records of Human Exposome, Including Biotic/Abiotic Exposures and Its Implications in the Assessment of the Role of Environment in Chronic Diseases

“…Hazardous outcomes caused by environmental stressors to ecological health are determined not only by toxic properties, but also changes in the ecosystems, including indigenous biodiversity and community composition. eDNA is one of the most emerging critical biological resources in the field of ecotoxicology [ 11 ]. Sequencing and bioinformatic analysis of eDNA samples have been extensively used to comprehensively investigate changes in the ecosystem and use it as a barometer of ecological health [ 10 , 12 ].…”

“…The application of eDNA metabarcoding extends across many applications. This has provided a huge new tool and more relevant approaches for assessments of risks posed to ecosystems by hazardous agents [ 11 ]. Researchers are additionally able to sample organisms and life stages which elude traditional techniques.…”

“…Traditional biomonitoring of exposome using DNA is limited to chemically modified adducts in blood, urine, or saliva samples [ 29 ]. The approach for untargeted biomonitoring of human exposome is being developed by combining genome-wide association study (GWAS), epigenome-wide association study (EWAS), and exposure-wide association study together; however, the development of this combined approach is in the very beginning stage [ 11 , 29 ]. Moreover, how the temporal and spatial environmental exposures that modulate the normal genetic/epigenetic and how phenotypic changes in a cell leading to the development of a particular type of disease phenotype will be assessed by these approaches remain to be sorted out.…”

“…This exposome study used longitudinal monitoring of personal airborne biotic and abiotic exposures, including microbial and viral, chemical, and environmental stressors and followed the personal exposomes of individuals of several distinct geographical locations. DNA and RNA exposomes showed that the DNA sequence mutations and variations in individuals located in the same general geographical region are diverse and dynamic, and these molecular risk factors changing as a function of age and environment may contribute significantly to human health deficits [ 11 , 86 ]. In summary, these studies suggest that the combined eDNA/eRNA approach analyzing both genomic and epigenomic modifications with exposure profiles may help to decipher the molecular susceptibility at the individual levels and assessing the risk of biological, chemical, physical, and spatial/lifestyle related health deficits.…”