Introduction
Measuring the Exposome
Diet as a Modifiable Exposure
Health Impacts and Disease Pathways
Emerging Research and Future Tools
Conclusions
References
Further reading
This article explains how the sum of environmental and dietary exposures, known as the exposome, shapes human biology from conception to aging. It explores molecular pathways, including redox balance, NRF2 signaling, and epigenetic change, through which diet and pollution jointly influence disease risk and prevention.
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Introduction
The exposome refers to the full range of environmental influences that affect us from the moment of conception. It includes everything from the air we breathe and the water we drink to the foods we eat, the microbes in our gut, and the psychological stresses we experience. According to Vineis and Barouki, the exposome also involves social and economic inequalities that influence health trajectories through biological mechanisms such as chronic inflammation and metabolic alterations.
These inputs do not act alone. Pollutants interact with dietary patterns, microbiome composition, sleep, and social stressors to influence inflammation, hormones, metabolism, and neural signaling. Over time, such combined pressures can alter gene expression, immune tone, and organ resilience, steering health trajectories toward or away from disease. Understanding the exposome clarifies prevention targets that matter in everyday life today.1
This article demonstrates how the exposome (comprising pollutants, diet, microbiome, and stress) influences biology through Nuclear factor erythroid 2-related factor 2 (NRF2), Cytochrome P450 (CYP450), oxidative stress, and epigenetics, and how multi-omics, wearables, and artificial intelligence (AI) facilitate personalized prevention.
Measuring the exposome
Measuring the exposome blends high-throughput “omics” with real-world sensing and modeling. Untargeted metabolomics, typically using high-resolution mass spectrometry (MS) paired with liquid or gas chromatography, screens thousands of endogenous and exogenous small molecules in biofluids to reveal pathway shifts linked to health and disease. AI/ML-driven workflows now automate the alignment, normalization, and feature selection of these complex MS datasets, improving annotation and cross-study comparability. Proteomics and epigenomics add mechanistic layers, while wearable sensors capture time-stamped data on air, activity, location, and physiology that contextualize exposures.2
AI and machine learning align spectra, select informative features, and help annotate unknown chemicals, which is essential because many environmental compounds occur at low abundance and in mixtures. These computational techniques, often embedded in cloud-based exposomics platforms, support “functional exposomics,” a framework that links molecular responses with environmental exposures to clarify exposure–phenotype interactions.6
Two analytic approaches illustrate depth and source attribution: untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) detects pollutant metabolites across a wide chemical space, and stable isotope tracing with labeled nutrients pinpoints dietary origins and metabolic fate. Together, these tools create an integrated readout of what enters the body, how it is processed, and which molecular signatures forecast risk or resilience.2,6
Diet as a modifiable exposure
Diet can act as a lever, either buffering or amplifying the toxicity of pollutants. Higher dietary intake of antioxidant vitamins A, C, and E is associated with weaker links between ambient air pollution and incident diabetes mellitus in the United Kingdom (UK) Biobank, supporting the idea that antioxidants mitigate pollution-induced oxidative stress and metabolic dysfunction. This protective effect was strongest for vitamins C and E, suggesting nutrient-specific modulation of particulate-matter–related risk.3
Oxidative stress is a key pathway by which particulate matter and nitrogen oxides trigger lipid peroxidation, inflammatory signaling, endothelial injury, and insulin resistance, which provides biological plausibility for dietary antioxidant strategies.3,4
Mechanistically, nutrient–xenobiotic interactions converge in the liver: the NRF2-Kelch-like ECH-associated protein 1 (KEAP1) axis senses electrophiles and reactive oxygen species, then induces antioxidant response-element programs, including phase-II enzymes such as heme oxygenase-1 and nicotinamide adenine dinucleotide (phosphate), reduced [NAD(P)H] dehydrogenase [quinone] 1; these defenses work alongside the CYP450 enzyme systems to support xenobiotic metabolism and limit cellular damage
NRF2 also interacts with pathways regulating apoptosis, mitochondrial biogenesis, and redox-sensitive signaling proteins, such as PTEN and EGFR, thereby expanding its role beyond detoxification to encompass cell survival and metabolic adaptation.4 Within the exposome, the microbiome is a critical mediator: gut flora is recognized as an internal exposure that alters host redox tone and inflammatory responses, thereby shaping how diet and pollutants translate into systemic risk.3,4
Together, these lines of evidence position diet as a modifiable exposure that can upregulate endogenous defenses via NRF2-linked pathways, stabilize metabolic homeostasis under polluted conditions, and act through the gut–liver axis to influence real-world health outcomes.3,4
Health impacts and disease pathways
Epigenetic changes translate environmental exposures into lasting biology that can drive chronic disease. Two core mechanisms, deoxyribonucleic acid (DNA) methylation and histone acetylation, alter chromatin accessibility and gene expression; microRNA (miRNA) networks further fine-tune these transcriptional programs. According to Ho et al., epigenetic reprogramming can occur during critical developmental windows, including the embryonic, perinatal, and pubertal stages, when environmental exposures, such as endocrine disruptors or air pollutants, can permanently alter gene regulation.
Exposures rarely act once: dose, timing, and mixtures matter, with sensitive windows spanning fetal life through puberty.
In prenatal air pollution case studies, traffic-related polycyclic aromatic hydrocarbons have been linked to hypermethylation of child immune and metabolic genes, as well as global hypomethylation in cord blood, which correlates with later respiratory symptoms and neurobehavioral differences. This suggests that in utero air toxics epigenetically reprogram developmental pathways with downstream effects on cognition and behavior.5
Pesticides provide another example of a second pathway. Endocrine-disrupting fungicides, such as vinclozolin and other pesticide-like agents, can leave lasting marks on both germline and somatic epigenomes (altered promoter methylation; disrupted histone marks), with transgenerational persistence. These transgenerational effects underscore the exposome’s temporal reach, illustrating how early-life exposures can impact disease susceptibility across multiple generations.
These epigenetic marks influence neuronal stress and inflammatory signaling, creating a plausible link to neurodegeneration. Consistent with this, environmental toxicant literature places neurodevelopmental disorders and Parkinson’s disease through shared air- and chemical-exposure–linked epigenetic susceptibility, where immune, redox, and dopamine-pathway genes are prime targets. Together, these lines of evidence support the use of epigenetic signatures as exposure “memories” to stratify risk and guide prevention during pregnancy and throughout the life course.5
The role of the exposome in health throughout the life course
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Emerging research is integrating the exposome into multi-omics and longitudinal cohorts that repeatedly profile external contacts and internal biology across life stages. Price et al. propose distinguishing the exposome, defined strictly as the totality of external contacts, from “functional exposomics,” which integrates biological responses across omics layers to interpret the effects of exposure.6 Functional exposomics maps exposure–phenotype links by integrating high-resolution exposure measurements, metabolomics, proteomics, epigenomics, clinical data, and context such as weather, housing, and social stress, then testing associations across time to find critical windows and causal pathways.
Recent mother–child and single-participant studies show thousands of time-resolved links between personal environment and omic signals, foreshadowing precision environmental health. Next-generation tools will pair untargeted MS for the internal chemical exposome with wearables, geospatial feeds, and outcome-wide longitudinal designs, all connected through transparent artificial intelligence and standards.2,6
These advances enable a “personal exposome passport”: a continuously updated, time-stamped record of meaningful exposures and responsive biomarkers, summarized into actionable risk scores and decision aids. Such passports, if ethically deployed, could support public health surveillance and individualized feedback loops to encourage preventive behaviors while maintaining safeguards for privacy and equity.6
Conclusions
Prevention is the practical takeaway of exposome science. Integrating social, biological, and technological determinants provides a complete view of how environment and behavior interact with biology across the life course.1,6
There are three main priorities: first, strengthen dietary defenses with minimally processed foods rich in antioxidants, omega-3 fats, fiber, and diverse polyphenols that support redox balance and microbiome health. Second, reduce exposures at the source through clean air, safe water, low-toxic housing and workplaces, and smarter urban design. Third, personalize risk with exposure monitoring that links wearables, geospatial context, and multi-omics into privacy-preserving dashboards for timely feedback. These steps turn broad, hard-to-define risks into actionable steps, guiding clinicians, families, and policymakers toward earlier intervention, reduced pollution-related illnesses, and healthier trajectories throughout pregnancy, childhood, and aging.
References
- Vineis, P., & Barouki, R. (2022). The exposome as the science of social-to-biological transitions. Environment International. 165. DOI:10.1016/j.envint.2022.107312, https://www.sciencedirect.com/article/10.1016/j.envint.2022.107312
- Petrick, L. M., & Shomron, N. (2022). AI/ML-driven advances in untargeted metabolomics and exposomics for biomedical applications. Cell Reports Physical Science. 3(7). DOI:10.1016/j.xcrp.2022.100867, https://www.cell.com/cell-reports-physical-science/article/10.1016/j.xcrp.2022.100867
- Li, H., Cai, M., Li, H., Qian, Z.M., Stamatakis, K., McMillin, S.E., Zhang, Z., Hu, Q & Lin, H. (2022). Is dietary intake of antioxidant vitamins associated with reduced adverse effects of air pollution on diabetes? Findings from a large cohort study. Ecotoxicology and Environmental Safety. 246. DOI:10.1016/j.ecoenv.2022.114182, https://www.sciencedirect.com/article/10.1016/j.ecoenv.2022.114182
- Zheng, F., Gonçalves, F. M., Abiko, Y., Li, H., Kumagai, Y., & Aschner, M. (2020). Redox toxicology of environmental chemicals causing oxidative stress. Redox Biology. 34. DOI:10.1016/j.redox.2020.101475, https://www.sciencedirect.com/article/10.1016/j.redox.2020.101475
- Ho, S. M., Johnson, A., Tarapore, P., Janakiram, V., Zhang, X., & Leung, Y. K. (2012). Environmental epigenetics and its implication on disease risk and health outcomes. ILAR Journal. 53(3-4). 289-305. DOI:10.1093/ilar.53.3-4.289, https://academic.oup.com/ilarjournal/article/10.1093/ilar.53.3-4.289
- Price, E.J., Vitale, C.M., Miller, G.W., David, A., Barouki, R., Audouze, K., Walker, D.I., Antignac, J.P., Coumoul, X., Bessonneau, V. & Klanova, J. (2022). Merging the exposome into an integrated framework for “omics” sciences. iScience. 25(3). DOI:10.1016/j.isci.2022.103976, https://www.cell.com/iscience/article/10.1016/j.isci.2022.103976
Further reading
Further Reading
Last Updated: Nov 10, 2025