Exposomics for better environmental health

The focus for World Environment Day in 2025 (June 5) is on ending plastic pollution. Micro-plastics represent one of the many thousands of chemical, physical and biological hazards that lurk in the air, water and living spaces for which we have neither the sensory capabilities nor sensing technologies to measure exposure and assess health risks. Thus, reducing the environmental disease burden continues to be a daunting challenge for public health.

In India, rapid economic growth is increasing the scale and the complexity of environmental exposures and the interdependencies between the living environment and lifestyles. With India already accounting for nearly 25% of the global environmental disease burden, there is a need to develop newer paradigms for environmental management that rest on integrated health risk assessments.

These must include all environmental factors into the study of disease development. The piece-meal approaches that define our current framing on environment or health indicators are likely to exaggerate environmental health inequities and result in spiralling health costs. We must embrace new and cutting-edge scientific developments in the field of “exposomics” to gain a more complete picture of disease etiologies over the life course and develop holistic prevention strategies. Strategic investments in long-term environmental health surveillance that integrate novel environmental and biomonitoring efforts with digital health and data science platforms are critical.

Environmental disease burden

The World Health Organization (WHO) began estimating the environmental disease burden in 2000, which is the basis for the modern estimation approach being adopted in the Global Burden of Disease, Injuries, and Risk Factor (GBD) study. Each cycle of the GBD identifies risk factors with the greatest attributable health burden. In the latest cycle (2021) that included 88 risk factors, environmental and occupational (OEH) risk factors in the GBD were responsible for 18.9% (12.8 million) of global deaths and 14.4% of all disability-adjusted life years (DALYs), led by ambient PM2.5 air pollution (4.2% DALYs, 4.7 million deaths) and household air pollution from the use of solid fuels for cooking (3.9% DALYs, 3.1 million deaths).

In India, nearly three million deaths and 100 million deaths are attributable to occupational and environmental health (OEH) risks. OEH risk factors in India are also estimated to account for more than 50% of the attributable burden for non-communicable diseases including ischemic heart disease, stroke, chronic obstructive lung disease, lung cancer, asthma and, more recently, diabetes and chronic kidney disease. Risk factors such as lead exposures can have grave developmental health impacts for children under five, with India accounting for up to 154 million or 20% of the total estimated IQ points lost globally in children under five.

What are we missing? The GBD results provide a strong and robust body of evidence to initiate actions for cleaner air, safer water and better sanitation. However, the current environmental burden of disease addresses only a limited number (around 11) of categories of environmental risk factors as there is a paucity of human exposure data. Several environmental risk factors that can contribute to significant health burdens are currently not included in the GBD. These include various chemical exposures, risks from complex mixtures such as micro-plastics and solid waste and physical hazards such as environmental noise.

More importantly, environmental risk factors interact in complex ways with metabolic (high blood pressure or high fasting plasma glucose) and behavioural risk factors (smoking and unhealthy diets) as well as underlying genetic susceptibility and upstream health determinants (such as socio-economic status) to produce a health impact within populations. Risk estimates are often derived for single risk factors; while confounding is often well adjusted in long-term cohort studies, complex mixtures and interactions over a life course have not been adequately explored.

Finally, climate change can magnify hazards posed by multiple environmental risk factors, such as heat, air pollution, vector-borne diseases, storms and flooding, and wildfires. Climate change may reduce crop yields, reduce agricultural worker productivity, disrupt food security and affect food supply chains. Depression, anxiety and other mental health outcomes, driven by both ecological concerns and direct health impacts of climate-sensitive environmental risk factors such as fine particulate matter, are also important to consider. Several of these risk factors can occur together, resulting in compound events and synergistic effects. These hazards can further amplify health impacts among populations with inadequate access to health systems or healthy food systems. Methods and data are not yet available to support inclusion of these important risk factors in the global burden of disease assessments.

Thus, the current environmental burden of disease estimates are not only a conservative underestimates but also do not provide an adequate means of prioritising against competing risk factors to develop holistic, scalable preventive health strategies.

The human exposome

The global human genome project (1990-2003) revolutionised our ability to explore the genetic origins of disease. However, it also revealed the limited predictive power of individual genetic variation for many common diseases. Genetic factors for example, contribute to less than half of the risk of heart disease, which is a leading source of mortality.

The success in mapping the human genome has fostered the complementary concept of the “exposome”. The exposome is defined as the measure of all the exposures of an individual in a lifetime and how those exposures relate to health. Traditional environmental health studies include hypothesis-driven methods which have focused on one or a class of environmental exposures at a few time points. These fail to account for the complex interactions of exposures across the lifespan, on human health.

Exposomics aims to bridge this gap by understanding how external exposures from physical, chemical, biological and psycho-social environments interact with diet and lifestyle and internal individual characteristics such as genetics, physiology, and epigenetics to create health or disease. This would allow the generation of an atlas of exposure wide associations (EWAS) to complement genome-wide associations (GWAS) and enable discovery-based analysis of environmental influences on health. The exposome requires synchronisation of several inter-disciplinary technologies which include real time sensor based personal exposure monitoring with wearables; untargeted chemical analyses on human biomonitoring samples; testing on human-relevant micro-physiological systems (also known as organs-on-a-chip) wherein in vitro models replicate the structure and function of human organs or tissues to understand the mechanistic basis of biological response; and big data, and artificial intelligence (AI) to mine data and generate integrated pieces of evidence.

Given that capacities and resources to generate exposomics data are not widely available, an immediate need for the exposomic framework to become a reality is also the creation of a data ecosystem in which harmonised data can be found, accessed, and shared through sustained and interoperable data repositories.

Mainstream environment within health

Exposome frameworks may seem implausible or irrelevant in India where the implementation of environmental health management programmes faces numerous hurdles. But, leapfrogging to technology and data-driven approaches is not new to the health sector. Exposomics offers unprecedented potential to mainstream environmental risks within public health programmes by generating more accurate predictive models for many chronic diseases while also enabling precision medicine. Unbridled investments in capacity building and synchronising available analytical, environmental and public health infrastructure offer the promise of addressing the concerns of our populations with unprecedented cost-effectiveness. The time is ripe for the Indian environmental health community to engage and contribute to the global momentum on the science of exposomics.

Future celebrations of World Environment Day may soon focus on why the human exposome project can be the best prescription for holistic prevention efforts that preserve and promote health equity.

Dr. Kalpana Balakrishnan is Dean (Research), Sri Ramachandra Institute of Higher Education and Research (SRIHER), Chennai