How environmental factors could influence disease and drugs

Studying lifetime exposures, also known as the “exposome,” offers a new perspective on how environmental and social factors impact disease pathways and overall well-being, and could impact the way pharmaceuticals research medicines.

The Centers for Disease Control and Prevention (CDC) defines the exposome as “the measure of all of a person’s exposures over a lifetime and how those exposures relate to health.” Amid a global spotlight on climate change, research into the exposome has exploded in recent years and become more relevant than ever.

In 2020, the EU launched the European Human Exposome Network (EHEN) to address environmental and health-related issues. EHEN has nine major projects carried out by 126 research groups in 24 countries. The initiative has received €106 million (US$105.5 million) from the European Commission to achieve the goal of understanding the impact of environmental and social pressures on health.

A deeper understanding of the exposome could help research into atopic diseases and allergies in particular. The ultimate goal of exposome research is to identify genetic and environmental risk factors, how together they make up a disease’s overall risk, its prognosis, and a patient’s need and susceptibility to various treatments, says Dr. Marc Rothenberg of the Cincinnati Children’s Hospital. When that happens, “[We] can intervene with various drugs and influence the natural course of the disease.”

This week, on April 34, scientiststh The annual conference of the International Society for Environmental Epidemiology (ISEE 2022) will examine the wide range of research on the exposome and its possible applications in health science. dr Sylvain Sebert, the project coordinator of Longitools, one of the EHEN projects, describes its purpose as “the use of exposomal research to explore the relationship between environmental factors, particularly pollution and other toxic factors, and the risk of cardiovascular and cardiovascular diseases to understand the course of life.”

Illustration of the exposome

In 2005, cancer epidemiologist Dr. Christopher Wild first introduced the concept of the exposome, which has now become a thriving field of research. Modeled on the Human Genome Project, exposome research aims to map all exposures affecting the human body throughout life to improve health outcomes. Research into the exposome also aims to understand the effects of environmental stresses in order 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, a biochemist and molecular biologist, heads Inserm Unit 1124, a research unit studying environmental toxicity, therapeutic targets, cellular signaling, and biomarkers. Barouki’s research involves using an AI-based tool to find chemical exposures associated with diabetes and link them to significant events and adverse event pathways (AOPs). “This is mostly done through text mining [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 examined the persistent chemicals associated with breast cancer metastasis. In this study, adipocyte cells from the tumors of over 100 women were examined, and after chemical analysis, the researchers found that the chemical dioxin, a by-product of many manufacturing processes, correlates with an increase in tumor size. Further in vitro The study concluded that dioxin increases the incidence of breast cancer tumor metastasis by inducing the expression of a cancer stem cell marker.

The EHEN project REMEDIA 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 (e.g. cigarette smoking) can have differential effects on CF and COPD phenotypes. To understand this variability, REMEDIA conducts epidemiological and experimental studies. On the epidemiological side, “we are studying the effect of these factors on COPD development in five cohorts of patients and we have access to the French CF registry,” says Lanone, who is also involved in GEIC20, an interdisciplinary team at Mondor Biomedical research institute, Creteil, France. On the experimental side, researchers expose mice to various factors such as air pollution, stress and physical activity.

A deeper understanding of disease pathways opens a door for the development of new drugs and treatment algorithms. By understanding the exposome, Barouki says, “you get a better understanding of how a chemical works, what proteins are involved, and what negative pathways are activated…which means maybe you can look at that pathway to develop a drug.”

In the field of atopic diseases and allergies, researchers have focused on integrating new exposome findings into precision medicine approaches. “Atopic disease is a complex trait, meaning there are genes and environmental factors that interact to produce different responses in specific individuals,” Rothenberg said. “The ultimate goal is to identify genetic and environmental risk factors and how they combine to form an overall disease risk that can affect prognosis, a patient’s susceptibility and their need for different treatments,” he adds.

Rothenberg and Mersha predict that understanding “omics” like the exposome could become crucial for the future of precision medicine. Phenotype penetration will be of paramount importance in the future not only for precision medicine in terms of targeting specific signaling pathways, but also for personalized drug responses and variability, he says.

Climate change and health inequalities

In addition to drug development, exposome research can have broader implications for human health. One such area that affects environmental factors is weather changes and air pollution. PM2.5 refers to fine particulate matter that is 2.5 microns in size and is associated with the disease pathology of asthma, COPD, coronary artery disease, stroke, lung cancer and more. These particles are small enough to pass through the lungs to the bloodstream and organs, and are typically released during activities such as heating and generating electricity in the home. The government has made great efforts to reduce the amount of PM2.5 particles in the air.

dr Tesfaye Mersha, a professor of pediatrics at the University of Cincinnati, says mapping these particles and other aspects of the exposome is difficult. “The problem is that the technology to map the exposome is not that mature and the measurement is very limited in some respects.” However, he notes that solving this problem in mapping environmental pressures was important, and says : “We need to consider it in our disease control prevention strategies, including precision medicine.”

Furthermore, Sebert describes the importance of such data by saying: “It is important to look at how environmental inequality relates to health inequality.” Longitools leads epidemiological studies and aims to develop new monitoring and forecasting methods and planning, among other things support new EU health and environmental policies, says Sebert.

Handling large amounts of data

Despite the potential importance, the volume of exposome data is slowing the process of their widespread use in the development of new drugs and the implementation of new guidelines.

Of the wide range of chemical exposures that exist, scientists have little understanding of 10,000 or 20,000 chemical exposures, Barouki says. “[The] The big challenge of the exposome is that it’s too broad and we can’t know everything, but we shouldn’t expect to study and map everything; we should try to do as much as possible,” he says.

Despite the daunting task ahead of mapping the exposome, researchers are optimistic about the potential implications of such knowledge. Regarding the exposome, Sebert adds: “I’m very optimistic that this offers a better way to improve and understand health in a more empirical way. Knowledge is improving, so there’s no reason why treatment can’t improve as well.”


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