Exposome: how the environment affects our health

Highlights:

‍

• Exposome is a concept that unites all possible environmental exposures, including chemical agents, stress, diet, air and water quality, and more
• Exposome is a counterpart to the genome, with both playing a role in defining human health. However, exposome is thought to have a larger impact on disease development
• Exposome relies on four primary environments: natural, built, social, and policy
• Monitoring exposome is an essential strategy in understanding and preventing chronic diseases and promoting longevity

‍

Introduction

‍

It is generally accepted nowadays that human health, longevity, and well-being rely on a variety of factors. While some health aspects are strongly linked to genetics, the environment equally determines the probability of beneficial outcomes. The exposome paradigm unites all nongenetic factors influencing health and disease, from chemicals and infectious agents to psychosocial stress. Understanding and systematizing these influences can be utilized both to assess risks and promote health. Nowadays, epidemiologists mostly rely on questionnaires to characterize “environmental exposure”. The exposome paradigm suggests a more encompassing, quantitative, and robust approach.

‍

Why we need to understand exposome 

‍

The original term “exposome” was coined relatively recently, in the 2000s, by Wild (1). He defined it as the sum of all environmental exposures, which also included diet, lifestyle, and endogenous sources. Exposome was regarded as a term complementary to genome and proteome, covering organism interactions on yet one level.

The importance of understanding exposome spurs from the generally recognized fact that the majority of chronic diseases result from the combination of exposure to chemical and physical stressors and human genetics. Some researchers estimate the influence of the environment to constitute up to 70-90% of risks (2,3). Such effects are also influenced by climate, lifestyle, and socioeconomic characteristics (4). All the environmental factors can thus be collectively considered environmental stressors. Large-scale epidemiological research allowed the accumulation of a large body of data on the causes of disease. However, these exposure data are often incomplete, non-standardized, and far from accurate. Exposome approach addresses and attempts to overcome these limitations by employing large-scale data analysis and an arsenal of modern detection techniques.

‍

What are we exposed to?

‍

In regard to health, exposures can be classified by the type of environment (5):

‍

• Natural,

The natural environment includes factors such as the quality of air, water, soil, and food. These factors can impact a variety of biological responses, including inflammation, reactive oxygen species, and protein/DNA adduct formation. Another factor that can be included in this category is chemical contamination. Exposure to “low-quality” natural environment and dangerous pollutants has been linked to multiple conditions, from cancer to type 2 diabetes. Chemical contamination is of special concern, with the major sources of pollution being air-borne particles, polycyclic aromatic hydrocarbons, volatile organic compounds, and heavy metals, among others (6). The sum of the chemical exposures can be regarded as the chemical exposome.

‍

•  Built

‍

The built environment includes everything that comprises the conditions of living – the quality of housing, spaces for communication and socialization, access to recreational areas, and working conditions. Deficiency in any of these commodities influences cortisol levels (through experienced stress) as well as sex hormone levels. Poor living quality (high or low temperatures, mold, low quality of drinking water), lack of resources, and social interactions are linked with multiple chronic conditions, especially cardiovascular and psychological (7). 

‍

• Social

‍

The social environment envelops a range of variables, such as rates of discrimination, poverty, crime, violence, and unemployment, as well as access to education, capital, health care, and law services. An unfavorable social environment excludes people from the ability to access healthier resources (such as food) adequately and accordingly impacts their ability to live a more longevity-supporting lifestyle. Adverse effects (8) include chronically increased adrenaline, vasoconstriction, altered brain plasticity (due to chronic stress), and increased pro-inflammatory cytokine secretion. 

‍

• Policy

‍

Finally, the policy environment addresses the impact which the government structures, laws, and regulations have on human health. This includes the impact of factors such as the level of corruption, voting rights, and the ability to participate in public discussion. Adverse effects on this level include changes in neurotransmitter levels (e.g., dopamine, serotonin, GABA). Chronic exposure to unfavorable conditions might lead to emotional insecurity and mental health deterioration. Additionally, changes in the policy environment directly influence all the other areas, leading, for example, to the changed location of farmer’s markets and thus easier access to healthy food (9).

‍

Choosing the right timeframe

‍

To employ the exposome paradigm, researchers are aiming to study the small molecules that get into the body due to exposure and their influence on biological pathways, which can impair health. Adverse effects can be linked to the concentration of exogenous or endogenous molecules circulating in blood and lymph. To measure the exposome, Rappaport and Smith suggested that the internal chemical environment of the body should be monitored during certain windows of exposure (10). This monitoring concept overcomes the traditional approach to population studies of diseases, which mostly recruited middle-aged subjects. Strong evidence suggests that the risk of diseases is influenced by (11):

‍

• Early exposure, including a baby being in the womb,
• Critical life stages that can bear long-term effects (e.g., a period when a child acquires their first language),
• Sensitive periods that are susceptible to large effects (like the development of vision). 

‍

The sequence of critical and sensitive periods constitutes a chain of risks. Employing this concept in practice means assessing multiple life stages and repeating various biomarker measurements at different time windows.

These measurements are conducted by monitoring the effects of chemical and nonchemical stressors on the body via signaling of the abovementioned small molecules, which are able to alter cellular activity and physiological processes. An example of nonchemical exposure could be emotional stress that makes the adrenal gland release adrenaline and other hormones into the blood, increasing breathing, blood pressure, and heart rate. Adrenaline can be monitored via analytical methods allowing to estimate exposure’s influence over time.

‍

Monitoring the exposure

‍

As we mentioned above, one of the ways to monitor exposome influence is through biomarkers. Multiple biomarkers can serve this purpose, and they can be roughly classified into three groups (9):

‍

• Biomarkers of disease susceptibility indicate an increased sensitivity of a person towards a particular disease. These include well-known biomarkers, such as glucose levels, triglycerides, cholesterol levels, apolipoprotein B, and others. These markers are abundantly used in diagnostics, and details on them can be found elsewhere.
• Biomarkers of exposure provide more specific information on affected pathways and associated risks. They allow measuring the toxicants directly in the blood, urine, tissues, etc. These biomarkers can be used to monitor heavy metal toxicants and polycyclic aromatic hydrocarbons and estimate risks of developing consequent conditions (i.e., renal ones) (12). 
• Biomarkers of Effect measure the level of whole-body, tissue, or organ function. For example, commonly measured biomarkers of cardiovascular risk (13,14) include glutathione peroxidase 3 assay, C-reactive protein, various interleukins, isoprostanes, and others.

‍

Though biomarkers are sufficiently specific, a single biomarker allows assessing a single factor's impact, thus covering only a small fraction of exposome. Currently, the biomarker approach is being adapted and further developed to provide a more global estimate of an organism’s response to exposome. High-resolution approaches (such as Liquid Chromatography/Mass Spectrometry) allow processing of a large number of samples detecting thousands of metabolites. This approach is being harnessed to explore the exposome’s impact on oxidative stress and various metabolic pathways. Novel methods (4) are being developed to allow similar processing of protein/DNA adducts, which would allow receiving a complex picture of how proteins like hemoglobin can be affected by reactive toxicants. Additional data from epigenomic and proteomic experiments can also be included to provide mechanistic links to potential health effects.

‍

Monitoring the environment

‍

The primary thing, however, that can be adapted from the exposome paradigm is the necessity to care about the environment. The recent advances in pollution monitoring technology allow for personal monitoring. An excellent example of that can be air pollution monitoring. Coupling novel air pollution monitors with GPS and accelerometry from smartphones together with personal patterns makes it possible to locate the pollution exposure and assess the contribution of the micro-environment (15). Solutions are also being developed for water and food monitoring that would allow estimating the risks on the go (16). Satellite modeling can be used for purposes such as an extension of exposure models to areas not covered by other sources of information.

‍

Conclusions – long but right way to go

‍

Exposome is a relatively new concept, which definitely has challenges in its development, such as in the identification of long-term effects due to the lack of the same degree of accuracy in exposure assessment as obtained in short-term experimental studies. However, the adoption and development of novel methods within this comprehensive approach would hopefully allow for better risk estimation and healthy lifestyle support. Even at the moment, based on the available data, people interested in health and longevity can try to carefully estimate their risks and strive for the healthiest environment possible.

‍

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 1;14(8):1847–50.
2. Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, et al. Environmental and Heritable Factors in the Causation of Cancer — Analyses of Cohorts of Twins from Sweden, Denmark, and Finland. N Engl J Med. 2000 Jul 13;343(2):78–85.
3. Willett WC. Balancing Life-Style and Genomics Research for Disease Prevention. Science. 2002 Apr 26;296(5568):695–8.
4. Vineis P, Chadeau-Hyam M, Gmuender H, Gulliver J, Herceg Z, Kleinjans J, et al. The exposome in practice: Design of the EXPOsOMICS project. Int J Hyg Environ Health. 2017 Mar;220(2):142–51.
5. Juarez P, Matthews-Juarez P, Hood D, Im W, Levine R, Kilbourne B, et al. The Public Health Exposome: A Population-Based, Exposure Science Approach to Health Disparities Research. Int J Environ Res Public Health. 2014 Dec 11;11(12):12866–95.
6. Misra BB. The Chemical Exposome of Human Aging. Front Genet. 2020 Nov 23;11:574936.
7. Compare A, Zarbo C, Manzoni GM, Castelnuovo G, Baldassari E, Bonardi A, et al. Social support, depression, and heart disease: a ten year literature review. Front Psychol [Internet]. 2013 [cited 2022 Aug 17];4. Available from: http://journal.frontiersin.org/article/10.3389/fpsyg.2013.00384/abstract
8. Bagby SP, Martin D, Chung ST, Rajapakse N. From the Outside In: Biological Mechanisms Linking Social and Environmental Exposures to Chronic Disease and to Health Disparities. Am J Public Health. 2019 Jan;109(S1):S56–63.
9. Juarez PD, Hood DB, Song MA, Ramesh A. Use of an Exposome Approach to Understand the Effects of Exposures From the Natural, Built, and Social Environments on Cardio-Vascular Disease Onset, Progression, and Outcomes. Front Public Health. 2020 Aug 12;8:379.
10. Rappaport SM, Smith MT. Environment and Disease Risks. Science. 2010 Oct 22;330(6003):460–1.
11. Ben-Shlomo Y. A life course approach to chronic disease epidemiology: conceptual models, empirical challenges and interdisciplinary perspectives. Int J Epidemiol. 2002 Apr 1;31(2):285–93.
12. Poręba R, Gać P, Poręba M, Antonowicz-Juchniewicz J, Andrzejak R. Relationship between occupational exposure to lead and local arterial stiffness and left ventricular diastolic function in individuals with arterial hypertension. Toxicol Appl Pharmacol. 2011 Aug;254(3):342–8.
13. Davies SS, Roberts LJ. F2-isoprostanes as an indicator and risk factor for coronary heart disease. Free Radic Biol Med. 2011 Mar;50(5):559–66.
14. Damy T, Kirsch M, Khouzami L, Caramelle P, Le Corvoisier P, Roudot-Thoraval F, et al. Glutathione Deficiency in Cardiac Patients Is Related to the Functional Status and Structural Cardiac Abnormalities. Kowaltowski AJ, editor. PLoS ONE. 2009 Mar 25;4(3):e4871.
15. Wacławik M, Rodzaj W, Wielgomas B. Silicone Wristbands in Exposure Assessment: Analytical Considerations and Comparison with Other Approaches. Int J Environ Res Public Health. 2022 Feb 9;19(4):1935.
16. Yang Y, Shi Z, Wang X, Bai B, Qin S, Li J, et al. Portable and on-site electrochemical sensor based on surface molecularly imprinted magnetic covalent organic framework for the rapid detection of tetracycline in food. Food Chem. 2022 Nov;395:133532.

‍