Exploring the Exposome: How Our Environment Shapes Our Health

We all know that environmental and lifestyle factors impact our health, but what role do our genes play? In an era where personalized medicine and genomic research are driving healthcare innovation, we now have the tools to delve deeper into the complex relationship between our environment and our genes. Helping to uncover this mystery, the exposome is a lens through which we can examine how external and internal exposures affect our health throughout our lives.

The exposome encompasses all the environmental factors we are exposed to – from the air we breathe and the food we eat to the lifestyle choices we make. By studying the exposome, researchers can identify the cumulative effects of these exposures and how they interact with our genes to influence health outcomes. This holistic approach can lead to more effective prevention strategies, personalized therapies and a better understanding of disease etiology.

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Figure 1. The three primary domains of the exposome. These general and specific exposures combine to influence biological responses throughout an individual’s life. Adapted from Barcelona Institute for Global Health[1]

Here we’re putting the exposome in the spotlight. We’ll see how genomics and other omics technologies are providing the speed and depth of analysis required to drive this exciting and burgeoning area of research forward, helping to bridge the gap between genetics and environmental factors.

What is the Exposome?

First introduced by Dr. Christopher Wild in 2005 [2], the exposome encompasses every environmental exposure an individual has encountered from the moment of conception. This broad definition includes three primary domains:

1. General External Environment: This includes larger-scale factors such as urban versus rural living environments, climate variations, and socioeconomic status. These elements can significantly influence health and well-being, shaping lifestyle choices and access to healthcare and resources.
2. Specific External Environment: These are direct exposures such as dietary habits, physical activity levels, tobacco smoke, pollutants, and infections. These specific exposures are often more easily identifiable and measurable, yet their interactions and cumulative impacts on health are complex.
3. Internal Environment: Internal biological processes, including metabolism, gut microbiota, inflammation, and oxidative stress also play a substantial role. These processes are influenced by external exposures and can mediate the body’s responses to environmental stressors.

The value of understanding the exposome lies in its potential to explain the etiology of chronic diseases. 70-90% of all chronic diseases, including asthma, cardiovascular disease and most cancers, have been linked to a combination of genetic predispositions and environmental factors [2]. By considering the full spectrum of exposures over a lifetime, it’s possible to identify causal relationships that might be missed when only looking at isolated factors.

From the exposome to our genes via epigenetics

At the nexus of exposome research and genetics lies the field of epigenetics, which is the study of changes in gene activity that do not involve alterations to the DNA sequence itself. Epigenetic mechanisms, such as DNA methylation and histone modification, play crucial roles in regulating gene expression. These non-genetic molecular changes modify the DNA’s physical 3D organization and its interaction with nuclear machinery, influencing the readiness with which certain genes can be expressed [3].

The best-studied epigenetic mechanism in humans is DNA methylation. This involves the addition of a methyl group to a cytosine base located upstream of a guanine base in a DNA sequence, a combination known as a CpG site. This process can suppress gene expression and represents a key mechanism through which environmental factors exert their influence on our genome.

Most research in this area focuses on identifying individual or clusters of CpG sites associated with specific risks or outcomes, such as smoking or birth weight. For instance, exposure to air pollution can lead to DNA methylation changes that affect genes involved in inflammation and cancer development [4]. Similarly, tobacco smoke exposure is linked to epigenetic modifications associated with lung disease, cardiovascular problems, and other health issues.

Epigenetics also considers the importance of dose, duration, composition, and the window of exposure in remodeling an individual’s epigenetic landscape and disease susceptibility. For example, low-dose, chronic exposures may have different effects compared to high-dose, acute exposures. Early-life exposures, particularly during critical developmental windows, can have lasting effects on gene expression and health, setting the stage for disease risk later in life. These early epigenetic changes can be further modified by lifelong exposures, continuously influencing disease susceptibility and health outcomes [5].

Another fascinating aspect of epigenetics is the concept of transgenerational effects through germline transmission. This means that epigenetic modifications induced by environmental exposures can be passed down to subsequent generations, potentially affecting their disease risk and health outcomes [6].

Understanding these epigenetic mechanisms is critical to comprehending the full impact of the exposome on health – alongside genomic, proteomic and metabolomic research, we’re beginning to bridge the gap between the dynamic influences of the environment and our health.

Want to explore the world of epigenetics further? Read our epigenetics blog

Figure 2. Chronic exposure to urban pollution can lead to lasting effects on gene expression and health for entire populations.

Challenges in exposome research

Given the vast scope of the exposome, encompassing all environmental exposures, there are unavoidable challenges in its research. Common hurdles faced when studying the exposome include:

• Accurate tracking of environmental exposures: Capturing the vast array of environmental exposures accurately over time is challenging. Environmental exposures can change over an individual’s lifetime, making it difficult to attribute a physiological change to a single stressor. In encompassing all environmental exposures, the exposome can reveal broader trends and patterns.
• Dynamic nature: The exposome’s complexity is compounded by its variation over our lifetime, necessitating longitudinal studies. For example, childhood exposures may have long-term health implications that manifest only in adulthood, such as increased risk of diabetes or cancer. Long-term studies must also account for lifestyle changes, such as changes in diet, physical activity and occupational hazards, to provide a comprehensive understanding of the exposome’s impact on health over time.

• Biological response measurement: Understanding how these exposures translate to biological responses is no easy task, and demands advanced tools and methodologies. Leveraging high-throughput sequencing technologies and omics approaches (e.g., genomics, proteomics, metabolomics) can be the most effective way to study how chemical exposures influence gene expression, protein function, and metabolic pathways.

Navigating these challenges is essential for advancing exposome research. Thanks to the emergence of next generation sequencing technology and multiomics approaches, we have unlocked the ability to resolve environmental impacts on our genetics like never before.

The value of omics in exposome research

Genomics technologies, particularly high-throughput screening platforms, have provided the speed and depth of analysis required to make large-scale exposome studies viable. The high-resolution and broad genome coverage provided by today’s genome sequencing platforms is crucial for capturing the dynamic and complex nature of the exposome.

In addition, further “omics” technologies can also be integrated with genomic studies to gain a more comprehensive view of how environmental exposures affect biological pathways and networks. This comprehensive approach can help decipher complex interactions between genes, proteins, metabolites, and environmental factors.

The HELIX Project

The Human Early Life Exposome (HELIX) project is a multi-center study investigating correlations between environmental hazards that mothers and children are exposed to and the health, growth and development of their children. This ambitious project collected and analyzed multiomics profiles (genome, methylome, transcriptome, proteome, and metabolome) of 1301 mother-child pairs during pregnancy and childhood [7].

The researchers conducted an Exposome-omics-Wide Association Study (ExWAS), investigating over 100 different chemical, outdoor, social and lifestyle exposures in pregnancy and childhood. They identified a total of 1170 significant associations between exposures and molecular features: In pregnancy, maternal smoking was found to be a significant predictor of DNA methylation changes in children. Among the most common childhood chemical exposures detected were copper and organochlorine compounds, thought to primarily arise from diet and pesticides.

Interestingly, the weather was also found to play a part – meteorological factors were linked to serum metabolites and plasma proteins, reflecting potential influences on thermogenesis and circadian rhythms. This study not only highlights the importance of early life exposure on our health, but stands as a fantastic example of the scale and depth of analysis that can be achieved with modern omics platforms. The study data from the HELIX Project is still under investigation in 2024 – a summary of findings can be found on the HELIX Project’s web app: ttps://helixomics.isglobal.org/

Omics technologies are providing an unprecedented understanding of the underlying environmental factors that contribute to disease etiology. Looking to the future, exposome research will help to inform personalized therapies, where interventions can be tailored to an individual’s unique exposome profile.

Exposing the exposome

Unravelling the exposome presents a unique opportunity to understand how our environment shapes our health. This emerging field offers a comprehensive approach to identifying the cumulative effects of environmental exposures and their interactions with our genes. By leveraging advanced epigenetics, genomics, and multiomics technologies, researchers are beginning to decipher the complex mechanisms linking these exposures to various health outcomes.

Looking to the future, exposome research has the potential to uncover new environmental links to disease, and could be valuable in informing public health policies by highlighting the need for cleaner air, safer food, and healthier living environments.

Eremid^® is at the cutting edge of genomics research. We can provide the expertise and technological prowess necessary for groundbreaking exposome analysis. Our comprehensive suite of services covers the latest in genomics sequencing technologies – including Illumina short-read sequencing and both PacBio HiFi and ONT long-read sequencing, transcriptomics services, as well as specialized epigenetics technologies like whole genome methylation sequencing. By harnessing the power of omics technologies, we can uncover the secrets of the exposome together and elevate public health.

References

1. Barcelona Institute for Global Health (2020). Available from: https://www.isglobal.org/en/-/el-exposoma-comprendiendo-el-efecto-del-entorno-en-nuestra-salud
2. Wild, C. P. (2005). Complementing the genome with an “exposome”: the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomarkers Prev, 14(8), 1847–1850. https://doi.org/10.1158/1055-9965.EPI-05-0456
3. Ng, J. W. Y., Felix, J. F., Olson, D. M. (2023). A novel approach to risk exposure and epigenetics-the use of multidimensional context to gain insights into the early origins of cardiometabolic and neurocognitive health. BMC medicine, 21(1), 466. https://doi.org/10.1186/s12916-023-03168-z
4. Go, Y. M., Weinberg, J., Teeny, S., Cirillo, P. M., Krigbaum, N. Y., et al. (2023). Exposome epidemiology for suspect environmental chemical exposures during pregnancy linked to subsequent breast cancer diagnosis. Environment
5. Schrott, R., Song, A., & Ladd-Acosta, C. (2022). Epigenetics as a Biomarker for Early-Life Environmental Exposure. Current environmental health reports, 9(4), 604–624. https://doi.org/10.1007/s40572-022-00373-5
6. Lee, G. S., Conine, C. C. (2022). The Transmission of Intergenerational Epigenetic Information by Sperm microRNAs. Epigenomes, 6(2), 12. https://doi.org/10.3390/epigenomes6020012
7. Maitre, L., Bustamante, M., Hernández-Ferrer, C. Thiel, D. Chung-Ho, E.L., et al. (2022). Multi-omics signatures of the human early life exposome. Nature Commun, 13, 7024. https://doi.org/10.1038/s41467-022-34422-2