Imagine the year 2050. During routine visits, patients provide blood and urine samples, their zip code, and information about their lifestyle and habits. The samples reveal nutrients and medications they have taken, infections they have experienced and chemicals they have encountered. A person’s location adds information about air pollution, noise and other environmental exposures.

Combined with genomic data, these measurements could help clinicians calculate an individual’s disease risk and identify treatments or preventive measures best suited to slow or even stop disease progression.

That is the future that exposome researchers are working to create.

What is the exposome?

The exposome is the totality of environmental exposures and lifestyle factors that, together with genetics, shape a person’s risk of developing common diseases such as cancer, heart failure, diabetes and dementia. The term was coined in 2005 by Christopher Wilde, a retired cancer epidemiologist at the International Agency for Research on Cancer in Lyon, France.

“There is a dire need to develop methods with the same precision for individual environmental exposures as for individual genomes,” Wilde said.¹

Between 70% and 90% of the risk of developing chronic diseases is attributed to environmental exposures.² “Genetics loads the gun, but environment pulls the trigger,” said Francis Collins, former director of the National Institutes of Health (NIH) in Bethesda, Maryland.

Environmental exposure can switch certain genes on or off. These epigenetic changes can contribute to disease. For example, cigarette smoke can suppress tumour-suppressor genes and increase cancer risk.

“Care cannot be individualized unless lifestyle factors, diet, medications, environmental exposures, and other factors are addressed,” says Gary Miller, director of the Center for Innovative Exposomics at Columbia University in New York City.

Each person’s exposures and genetic profile contribute to a unique disease risk. Researchers say exposomics could help fill in the missing details needed to make precision medicine more effective.

However, measuring the exposome is difficult. Researchers need to assess as many non-genetic disease factors as possible by combining data from biobanks, long-term cohort studies, diet and medication research, physical-activity studies and environmental datasets such as geospatial models of air pollution.

How scientists measure environmental exposures

Some exposures can be measured through biomarkers, including sugars, proteins and chemical breakdown products in the blood and urine. These markers can reveal biological changes linked to environmental triggers.

“There are traces of past exposures left in the body,” Miller said. Persistent organic pollutants, for example, can remain in fatty compounds called lipids in the blood. Smoking can also add chemical tags, or epigenetic markers, to DNA that persist even after 30 years of not smoking.

Advances in high-throughput mass spectrometry have made it easier to analyze large numbers of blood samples and track proteins and metabolites. These measurements can be combined with transcriptomics, which reveals which genes are active inside cells, to identify and validate biochemical markers associated with disease and environmental exposure.

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Why exposomics matters for precision medicine

Exposomics has attracted scepticism. Some critics argue that it is simply a new name for environmental epidemiology, which often examines the effects of individual exposures. Others say it is impossible to measure the totality of human exposure.

Even so, interest in exposomics has grown rapidly. A search for “exposome” in the PubMed literature database found at least 830 papers published in the year described, compared with 261 papers in all of 2020.

Scientists are now coordinating efforts to develop standards and protocols and to build the capacity to monitor changing exposures over time. Kyle Walsh, director of the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina, said enthusiasm is growing at the NIH for a multiyear, multimillion-dollar Human Exposome Project.

The proposed project would provide a comprehensive, molecular-level assessment of environmental exposures to identify the factors that most strongly drive disease.

If successful, exposomics could usher in a new era of precision medicine and precision prevention.

Large-scale studies link exposures to disease risk

In March, exposomics researcher Chirag Patel of Harvard Medical School in Boston, Massachusetts, and his colleagues published one of the largest studies to match environmental exposure with disease risk.³

Using data from 10 cohorts in the 55-year National Health and Nutrition Examination Survey, the researchers compared 619 exposure markers, including blood mercury and vitamin B12 levels, with 305 measurable characteristics such as lung function and blood-sugar levels.

When considered individually, environmental exposures accounted for less than 1% of the variation in disease outcomes. When researchers combined the effects of 20 exposures, however, the figure increased to an average of 3.5%.

Although the increase may seem small, it rivals the predictive power of genetic variants that influence disease. The findings support the need to study real-world exposures to improve disease management, Patel said.

For example, 43% of participants’ triglyceride levels — a marker associated with cardiovascular disease — were explained by a unique combination of 20 exposures, including trans fats and polychlorinated biphenyls. Advanced cellular senescence, which involves structural or molecular damage to cells, was most strongly associated with smoking, limited physical activity and exposure to heavy metals.

Patel says the next step is to determine which exposures are most important and which ones disrupt biological pathways. If population-level studies can link environmental exposures to changes in biological pathways, the findings could eventually help predict outcomes for individuals.

For instance, studies examining links between cell mutations and air pollutants could help identify people at increased risk of lung cancer.

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Biobanks and artificial intelligence could unlock the exposome

Biobanked samples and long-term cohort studies will be crucial to this work. Walsh suggests that the All of Us programme, an NIH effort to collect health data from more than 1 million US volunteers, is an obvious starting point for the Human Exposome Project.

All of Us has enrolled 883,000 participants to date, making it the world’s largest integrated genomic and electronic health-records database. It stores more than 600,000 physical measurements and 747,000 responses to social, behavioural and environmental surveys.

The fundamental challenge is connecting these data points and understanding how they translate into an individual’s disease risk. “This is a data analysis problem,” Walsh said. Artificial-intelligence tools could make the task more manageable.

High-resolution mass spectrometry of blood or urine typically produces a spectrum with 10,000 to 100,000 distinct peaks. Identifying and measuring the compounds represented by those peaks is one of the biggest bottlenecks in exposomics.

Machine-learning models can help sift through the data and decode the results. The structure of a chemical can also indicate its potential biological effects, allowing researchers to include previously unknown chemicals in disease-risk assessments.

With AI tools, researchers hope to expand the scale and scope of exposomics studies. Miller predicts that, over the next three years, scientists will conduct advanced exposomics research using data from about 100,000 people.

“If we did that for the 10 major human diseases, we would see which exposome profiles are associated with different outcomes in different diseases,” Miller said. Such information could help clinicians determine whose disease is likely to progress fastest or who is most likely to benefit from a particular drug.

Using exposomics to prevent disease

The clinical potential of exposomics is beginning to attract attention. The Exposome Scanning Facility in Leiden, the Netherlands, was established in 2024 to create exposome profiles for researchers and clinicians.

At present, exposome scanning can identify about 700 chemicals, including pesticides and flame retardants, said Roel Vermeulen, an exposome researcher at Utrecht University in the Netherlands and co-director of the facility.

Vermeulen estimates that this represents roughly 10% to 20% of the thousands of chemicals that result in significant human exposure around the world. “I strongly believe that you shouldn’t wait until you can measure everything,” he says.

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