The exposome is a newish concept that, in simple terms, refers to the measure of all the exposures of an individual from conception to death, and how those exposures impact the individual’s health. In this article, we will provide an overview of what is meant by the exposome and the field of exposomics. We will look at the various disciplines that contribute to that field, and some broad health-related questions that exposomics might help to answer. Lastly, we will touch on the benefits of incorporating microsampling methods into exposomics for cheaper and less invasive population-wide studies.

Firstly, what is the exposome?

The exposome was first introduced as a concept in 2005 by Dr. Christopher Wild, who was at that time Director of the International Agency for Research on Cancer. He coined

The exposome was first introduced as a concept in 2005 by Dr. Christopher Wild, who was at that time Director of the International Agency for Research on Cancer. He coined the term ’exposome’ based on the need to consider the environment in our understanding of human disease.

In his seminal editorial published in Cancer Epidemiology, Biomarkers & Prevention, Wild notes: “There is a desperate need to develop methods with the same precision for an individual’s environmental exposure as we have for the individual’s genome. I would like to suggest that there is need for an “exposome” to match the “genome.” This concept of an exposome may be useful in drawing attention to the need for methodologic developments in exposure assessment.”(1)

According to Wild’s original definition, ”the exposome encompasses life-course environmental exposures (including lifestyle factors), from the prenatal period onwards. Unlike the genome, the exposome is a highly variable and dynamic entity that evolves throughout the lifetime of the individual.” Other definitions have since been proposed, which reflect the transient nature of the exposures measured in exposomes.

Wild’s exposome concept considers three overlapping domains:

1. The general external domain, including factors such as urban–rural environment, climate factors and societal factors, stress and other factors
2. The specific external domain, including diet, physical activity and other lifestyle factors assessed at the individual level, as well as exposure to drugs, radiation, heavy metal exposure and associated toxicity, environmental pollutants and others
3. The internal domain, which encompasses individual genetics, metabolic processes, stress responses, microbiota, hormone signalling, aging and other biological processes

What can exposomics tell us about health and disease?

As the name suggests, exposomics is the field of the exposome, and the encompassing studies reply on a broad range of methods to measure internal and external exposures.

Although the field is relatively new and methods to study the exposome are still being debated and refined, exposomics is seen as an important tool in understanding the interplay between genetics (including epigenetics) and environmental factors in the development of diseases, in particular chronic conditions.

Exposomics studies typically aim to evaluate the long-term impacts of:

• Chemical exposures: to pollutants, food additives, heavy metals, and per- and polyfluoroalkyl substances (PFAS), also known as forever chemicals which are found in many standard household items such as non-stick cookware, water-repellent clothing, stain resistant fabrics and carpet, and others
• Exposure to physical factors: e.g., UV radiation, noise
• Exposure to lifestyle factors: diet, exercise, smoking, alcohol, stress
• Exposure to social factors: socioeconomic status, education

Genetics is estimated to account for about 10% of all known diseases, with environmental impacts as a whole believed to cause the remaining 90%.

By revealing links between disease risk and certain exposures, exposomics can help us to understand why some people get sick from certain exposures while others do not. Indeed, exposomics has already provided important insights into cardiovascular diseases, cancers, autoimmune diseases and others (2, 3, 4). As the field progresses, it is expected to contribute to personalised medicine, public health interventions, and environmental policies.

How can we study the exposome?

Not surprisingly, exposomics is a highly multidisciplinary field involving many different disciplines and methods, including but not limited to:

• Environmental scientists: Studying various environmental factors and pollutants
• Biologists:
  • By applying ‘omics’ tools such as genomics, metabonomics, adductomics (a new area of research that provides structural data on the about the impact of chemical exposures on DNA (DNA adducts) and proteins (protein adducts), lipidomics, transcriptomics, epigenomics and proteomics. Some leaders in the field have suggested that the study of metabonomics should be the sole focus, but this is still being debated. All of the ‘omics’ methods can shed light on how exposures affect biological systems, measure relevant biomarkers as well as reveal new biomarkers
  • Other analytical methods include immunoassays (e.g., ELISA), which are used to detect and quantify analytes (biological or exogenous) from human body samples such as blood, urine or other bodily fluids.
• Chemists: Analysing chemical compounds in the environment and the body
• Epidemiologists: Investigating patterns of exposure and health outcomes in populations
• Toxicologists: Assessing the harmful effects of heavy metals and environmental agents
• Geneticists: Examining gene-environment interactions
• Data scientists and bioinformaticians: Managing and analysing large, complex datasets to find statistical associations between exposures and their effects as well as the interaction between exposures and genetics.
• Clinicians: Applying findings to clinical practice and personalised health
• Policy markers: Developing interventions and policies based on exposomics research
• Engineers: Developing new technologies for exposure assessment, including sampling devices.

Microsampling as a practical solution to some of the challenges faced within exposomics

Exposomics is a challenging field for many reasons. Firstly, an individual’s exposome is highly variable and dynamic throughout their lifetime, which means that snapshot measurements taken at a single point in time are unlikely to provide meaningful data.

Another complicating factor is that an exposure that contributes to disease in one person may not have the same or any measurable impact on another person because of variations in genetics and other individual factors. Although there is no single solution to those challenges, faster sampling and testing technologies that facilitate non-biased, large-scale population studies for increased data collection and gathering will help to provide the knowledge base from which associations can be made.

In recent years, microsampling has gained traction as an alternative to whole blood sampling within diagnostics and disease monitoring, with validated applications in COVID-19 testing and research, diabetes monitoring, drugs of abuse testing and others.

More recently, microsampling was used to measure 25 different PFAS in human blood samples, using a combined liquid chromatography-mass spectrometry workflow. In that study, researchers in Italy used Capitainer’s volumetric blood sampling device Capitainer®B to collect 10 microliters of capillary blood (via finger-prick). The blood samples were subsequently dried and subjected to an extraction protocol suitable for the PFAS of interest. The researchers reported detecting PFAS concentrations between 2-100 ng/mL, which is suitable for monitoring exposure levels in at-risk populations. The analysis showed good accuracy and reproducibility, with the blood samples remaining stable for at least 4 weeks regardless of storage temperature (5).

The benefits of microsampling make this approach highly suited to large-scale population studies, e.g., minimal invasiveness (compared with venous blood draw), lower costs (since no phlebotomist is needed for sampling), easier sample storage and shipping since dried blood can be shipped as regular non-hazardous post, lower sampling volumes and ease of sampling which may increase participation in large-scale population studies.

Stay tuned for future articles about exposomics!

References

1. Wild CP. Complementing the genome with an ”exposome”: the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8):1847-50.
2. Bonanni A, Basile M, Montone RA, Crea F. Impact of the exposome on cardiovascular disease. Eur Heart J Suppl. 2023 Apr 21;25(Suppl B):B60-B64.
3. Sharif, R., Ooi, T.C. Understanding exposomes and its relation with cancer risk in Malaysia based on epidemiological evidence: a narrative review. Genes and Environ 46, 5. 2024.
4. Danieli MG, Casciaro M, Paladini A, et al. Exposome: Epigenetics and autoimmune diseases. Autoimmun Rev. 2024 Jun;23(6):103584.
5. Galletto M, Ververi C, Massano M, et al. Development and validation of the UHPLC-MS/MS method for the quantitative determination of 25 PFAS in dried blood spots. Anal Bioanal Chem. 2024 Nov;416(26):5671-5687.