How environmental factors might influence disease and medication
The study of lifetime exposures, also known as the ‘exposome’, offers new insight into how environmental and social factors affect disease pathways and overall well-being, and may influence how whose pharma researches drugs.
The Centers for Disease Control and Prevention (CDC) defines the exposome as “the measure of all of an individual’s exposures over a lifetime and how those exposures relate to health.” Amid the global spotlight on climate change, exposome research has exploded in recent years, becoming more relevant than ever.
In 2020, the EU launched the European Human Exposomes Network (EHEN) to tackle environmental and health issues. EHEN has nine large-scale projects that are executed by 126 research groups in 24 countries. The initiative has received 106 million euros ($105.5 million) from the European Commission to achieve the goal of understanding the impact of environmental and social exposures on health.
A better understanding of the exposome could in particular help research on atopic diseases and allergies. The ultimate goal of exposome research is to identify genetic and environmental risk factors, how they combine to form the overall risk of a disease, its prognosis, and a patient’s needs and susceptibility to different treatments, says Dr. Marc Rothenberg, of Cincinnati Children’s Hospital. As it happens, “[We] can intervene with different drugs and influence the natural history of the disease.
This week, scientists from 34e The annual conference of the International Society for Environmental Epidemiology (ISEE 2022) will explore the wide range of exposome research and its possible applications in the health sciences. Dr Sylvain Sebert, coordinator of the Longitools project, one of the EHEN projects, describes its goal as “using exposomal research to understand the relationship between environmental factors, including pollution and other toxic factors, and the risk of diseases cardiovascular and cardiometabolic across the course of life.”
Map the exposome
In 2005, cancer epidemiologist Dr. Christopher Wild first coined the term exposome, which has since become a burgeoning area of research. Like the Human Genome Project, exposomal research aims to map all exposures that affect the human body throughout life in order to improve health outcomes. Exposome research also aims to understand the effects of environmental exposures to mitigate the effects of climate change on human health. A wide range of tools ranging from bioinformatics programs to systems biology approaches are used to map the full extent of the exposome.
Dr. Robert Barouki, biochemist and molecular biologist, heads Inserm Unit 1124, a research unit that studies environmental toxicity, therapeutic targets, cell signaling and biomarkers. Barouki’s research involves using an AI-based tool to find chemical exposures associated with diabetes and linking them to meaningful events and adverse outcome pathways (AOPs). “This is done primarily through text mining the [adverse outcome] path. The tool develops a framework that links a molecular event to cellular events and adverse outcomes to identify meaningful associations.
Another of Barouki’s studies looked at persistent chemicals associated with metastasis in breast cancer. In this study, fat cells taken from the tumors of more than 100 women were analyzed and, after chemical analysis, the researchers were able to determine that the chemical dioxin, a by-product of many manufacturing processes, had a correlation with a increase in tumor size. Further away in vitro study concluded that dioxin increased the incidence of breast cancer tumor metastasis, by inducing the expression of a cancer stem cell marker.
The EHEN REMEDIA project focuses on how exposures affect cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). REMEDIA project coordinator Sophie Lanone, PhD, explains that common environmental risk factors (eg, smoking) can have varying effects on CF and COPD phenotypes. To understand this variability, REMEDIA conducts epidemiological and experimental studies. On the epidemiological level, “we are studying the effect of these factors on the development of COPD in five cohorts of patients, and we have access to the French registry of cystic fibrosis”, explains Lanone, who is also part of the GEIC20, a team interdisciplinary of Mondor Biomedical. Research Institute, Créteil, France. On the experimental side, researchers expose mice to different factors such as air pollution, stress and physical activity.
A better understanding of disease pathways opens the door to the development of new drugs and treatment algorithms. By understanding the exposome, Barouki says, “you better understand how a chemical works, what proteins are involved, and what negative pathways are activated…which means you can maybe look at that pathway to develop a drug.”
In the field of atopic diseases and allergies, researchers have focused on integrating new exposomic knowledge into precision medicine approaches. “Atopic disease is a complex trait, which means there are genes and environmental factors that interact to cause different responses in some individuals,” Rothenberg said. “The ultimate goal is to identify genetic and environmental risk factors, and how they combine to form an overall disease risk, which can influence prognosis, as well as a patient’s susceptibility and need for different treatments” , he adds.
Rothenberg predicts that understanding “omics” such as the exposome could become critical for the future of precision medicine. Phenotype penetration is going to be paramount not only for precision medicine in terms of targeting specific pathways, but also for personalized responses to drugs and variability, he says.
Climate change and health inequalities
In addition to drug development, exposomal research may have broader implications for human health. One such area involving environmental factors is that of climate change and air pollution. PM2.5 refers to particles with a size of 2.5 microns and is linked to the pathology of asthma, COPD, coronary heart disease, stroke, lung cancer, etc. These particles are small enough to pass through the lungs into the bloodstream and organs and tend to be emitted during activities such as home heating and power generation. The government has made significant efforts to reduce the amount of PM2.5 particles in the air.
Dr. Tesafye Mersha, a professor of pediatrics at the University of Cincinnati, says it’s difficult to map these particles and other aspects of the exposome. “The problem is that the technology for mapping the exposome is not that mature, and the measurement is very limited in some ways.” However, he argues that it was important to overcome this issue when mapping environmental exposures, saying, “We need to factor this into our disease control prevention strategies, including precision medicine.”
Further, Sebert describes the importance of this data, saying, “It is important to examine how environmental inequality relates to health inequality.” Longitools conducts epidemiological studies and aims to develop new methods for monitoring and forecasting and to help plan new European health and environmental policies, among others, Sebert explains.
Processing large amounts of data
Despite the potential importance, the scale of exposomal data slows the process of their large-scale use in the development of new drugs and the implementation of new policies.
Of the wide range of chemical exposures present, scientists only have a small understanding of 10,000 or 20,000 chemical exposures, Barouki says. “[The] the great challenge of the exposome is that it is too broad and that we cannot know everything, but we should not expect to dose and map everything; we should try to do everything we can,” he said.
Despite the daunting task ahead of mapping the exposome, the researchers are optimistic about the possible impact this knowledge could have. Referring to the exposome, Sebert adds, “I’m very optimistic that it provides a better opportunity to improve and understand health more empirically. Knowledge is improving, so there is no reason why treatment should not improve as well.