The exposome: a definition

The concept of the exposome was first proposed in 2005 by Christopher Paul Wild, a molecular epidemiologist who, among his various positions, directed the International Agency for Research on Cancer (IARC) in Lyon until 2018. With this term, Wild wanted to encompass all the environmental factors to which we are exposed from the very earliest stages of development, even before birth.

Within the exposome there are three overlapping domains:
a general external environment (e.g. the urban environment, climate, social conditions, stress, noise, artificial light);
a specific external environment (e.g. chemical contaminants, diet, physical activity, tobacco use, infections);
an internal environment (e.g. metabolic factors, the gut microbiome, inflammation, oxidative stress).

The exposome is therefore a dynamic system that keeps changing in the external and internal environment throughout the entire course of life.

Exposome and genetics

The Human Genome Project changed the way we understand diseases and helped prevent and treat them better. Today, however, we know that only 10% of diseases are due to genetics, while the rest is influenced by the environment. Stimuli, in fact, interact with the genetic characteristics specific to each human being, influencing their expression throughout life (through mechanisms called epigenetic). Environmental factors, which include both the substances we come into contact with and lifestyle-related behaviors, therefore determine health status and the risk of chronic diseases, including cardiovascular diseases, cancers and respiratory diseases.

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Exposome and aging

The concept of the exposome therefore offers the possibility of integrating data on the environmental component into the etiology of diseases related to aging, to improve our understanding of the predictive, risk and protective factors of complex and multifactorial chronic diseases. If we think, for example, of skin aging, a determining factor that falls within the exposome is UV rays.

Measuring the exposome

A key factor in understanding the exposome is the ability to accurately measure external and internal exposures and their effects on health. To analyze exposures to a specific external environment, questionnaires are used, supported by smartphone apps that act as consumption diaries or by sensors for physical activity and geolocation. Exposures to the general external environment, on the other hand, are assessed at the community level using environmental monitoring methods. Molecular omics techniques are certainly the best tool for studying the set of molecules and their effects on gene expression profiles (transcriptomics and epigenomics). Much scientific evidence shows that some epigenetic modifications (methylation and miRNA) are caused by exposure to toxic substances or environmental stress. The hope is to find a unique pattern that can characterize the entire exposome, to better understand the molecular bases linked to certain diseases. The challenge for the near future is to develop tools to manage enormous amounts of data that must be stored, analyzed and interpreted. An ever greater understanding of the exposome will lead to the development of strategies for prevention and for healthy longevity, to improve health policies.