How Your Environment Gets Under Your Skin to Shape Health and Disease
Imagine two children growing up in the same city, attending the same school, with similar genetic backgrounds. One develops asthma while the other remains healthy. A woman in her fifties, never a smoker, receives a lung cancer diagnosis. A factory worker finds himself constantly fatigued, his body seemingly aging faster than his years. What invisible forces might be at work in these scenarios?
For decades, we've understood that genetics play a crucial role in health outcomes. But the revolutionary science of exposure-induced disease susceptibility reveals a more complex and dynamic picture: our environment "gets under our skin" literally, altering how our genes function without changing the DNA sequence itself. From the air we breathe to the water we drink, from our workplaces to our stress levels, environmental exposures interact with our biological systems in ways that can either protect us or predispose us to disease.
"The overarching goal of my research program is to identify environmental factors that modify the epigenome and increase risk for disease throughout the life course. We're particularly interested in how toxic exposures affect susceptible populations including children and occupationally exposed workers." 1
This article will take you on a journey through the fascinating science of how our environments shape our health destinies, highlighting the groundbreaking work of scientists who are decoding these complex relationships.
Understanding how our environment influences health requires exploring several key scientific concepts.
If the genome represents all our genetic material, the exposome encompasses every environmental exposure we experience from conception to death.
Epigenetics - literally meaning "above genetics" - refers to molecular mechanisms that regulate gene expression without altering the underlying DNA sequence.
Why can two people with similar exposure histories have dramatically different health outcomes? The answer often lies in gene-environment interactions.
These interactions reflect the complex ways our genes interact with environmental factors to influence health 2 .
Connecting Chemicals to Immune Changes
To understand how exposure science works in practice, let's examine a landmark study published in Environmental Health Perspectives that analyzed data from the National Health and Nutrition Examination Survey (NHANES) 6 . This study exemplifies the comprehensive approach needed to decode the exposome's influence on health.
45,528 adult participants from NHANES surveys (1999-2018) with a mean age of 45.7 years, 51.4% female, and 69.3% Non-Hispanic White.
196 chemicals from 17 different chemical families measured in participants' blood or urine.
Eight key immune biomarkers assessed, including counts of lymphocytes, neutrophils, monocytes, basophils, eosinophils, red blood cells, white blood cells, and mean corpuscular volume.
Separate survey-weighted, multivariable linear regressions for each chemical and immune measure, adjusting for relevant covariates.
The analysis revealed striking connections between chemical exposures and immune system changes:
| Chemical Category | Specific Chemicals | Immune Biomarkers Affected | Health Implications |
|---|---|---|---|
| Smoking-related compounds | Cotinine | Mean corpuscular volume, red blood cell counts | Associated with increased cardiovascular risk |
| Metals | Lead | Red blood cell counts | Affects oxygen transport, potentially damaging multiple organs |
| Various chemical families | 71 individual chemicals (36.2% of those tested) | At least one of eight immune biomarkers | Widespread potential for immune disruption |
| Chemical | Exposure Source | Immune Impact | Measured Effect |
|---|---|---|---|
| Cotinine | Tobacco smoke | Increased mean corpuscular volume | 0.16 fL increase per doubling in concentration |
| Lead | Old paint, contaminated water | Increased red blood cell count | 61,736 more cells per μL per doubling in blood concentration |
| Multiple metals | Industrial pollution, diet | Altered various immune cell counts | Varies by specific metal |
This research is groundbreaking for several reasons:
The implications are profound - they suggest that our immune systems are constantly responding to countless environmental chemicals, potentially shaping our susceptibility to a wide range of diseases.
Research Reagent Solutions
To conduct cutting-edge exposure research, scientists rely on sophisticated tools and reagents. These materials enable precise measurement of exposures and their biological effects.
| Research Tool | Function | Application Example |
|---|---|---|
| B21R conjugates | Capture mpox-specific antibodies to avoid cross-reactivity with other poxviruses | Enabled development of specific serologic detection of mpox infection with 93% sensitivity and 98% specificity 5 |
| Small-molecule enzyme substrates | Yield color or light signals in diagnostic assays | Used in ELISAs and microbiological culture diagnostics to provide clear positive/negative readouts 5 |
| Antigens and antibodies | Detect immune responses to specific pathogens | Critical for developing tests for emerging pathogens like Nipah virus and differentiating between viral strains 5 |
| Biological matrices | Serve as controls in assay development and validation | Normal and disease-state plasma used to ensure test accuracy and reliability 5 |
| Epigenetic sequencing tools | Map DNA methylation patterns and histone modifications | Allow researchers to identify epigenetic changes linked to specific environmental exposures 2 |
These tools have become increasingly important as diagnostic challenges grow more complex. For example, during the recent mpox outbreak, standard PCR tests could detect the virus but couldn't easily distinguish between different strains. The development of specialized B21R conjugate peptides allowed researchers to create tests that could differentiate current mpox infections from previous smallpox vaccinations or other poxvirus exposures 5 .
The science of exposure-induced disease susceptibility is moving beyond the laboratory and into clinical practice through innovative approaches like personalized predictive modeling. Rather than using "one-size-fits-all" risk models, researchers are now building patient-specific models trained using information from clinically similar patients 4 .
In one study of diabetes onset, researchers used a technique called Locally Supervised Metric Learning to identify patients with similar clinical profiles, then built personalized logistic regression models to predict disease risk.
These personalized models outperformed traditional global models because they could capture risk factors particularly relevant to each patient's unique situation 4 .
Machine learning approaches are being applied to exposure-response analysis, with artificial neural networks serving as "universal function approximators" that can detect complex, nonlinear relationships between exposures and health outcomes that traditional statistical methods might miss 8 .
Perhaps most exciting is the development of exposome-based predictive models for major diseases. One recent study introduced a machine learning model that used 109 exposome variables - including physical measures, environmental factors, lifestyle choices, mental health events, and early-life factors - to predict cardiovascular disease risk.
The model performed comparably to traditional clinical models, identifying significant exposome factors including daytime naps, completed full-time education, past tobacco smoking, frequency of tiredness/unenthusiasm, and current work status .
The growing understanding of exposure-induced disease susceptibility represents both a challenge and an opportunity.
The challenge lies in recognizing the multitude of environmental factors that can compromise our health, often invisibly and cumulatively. The opportunity exists in harnessing this knowledge to develop more personalized approaches to disease prevention and health promotion.
As the research highlighted in this article demonstrates, we're moving toward a future where we can:
Identify individuals at highest risk from specific environmental exposures based on their genetic and epigenetic profiles
Develop targeted interventions to reduce the most harmful exposures at individual and population levels
Create personalized health recommendations based on a comprehensive understanding of each person's exposome
Advocate for policies that reduce the most dangerous environmental threats, particularly for vulnerable populations
The science makes clear that our health is not predetermined by our genes alone, nor is it solely determined by our environment. Rather, it emerges from the continuous dialogue between our DNA and our lived experiences - from the air we breathe to the stresses we endure, from the chemicals we encounter to the nutrients we consume.
By understanding these complex interactions, we can make more informed decisions about our health, shape public policies that protect the most vulnerable, and ultimately reduce the burden of environmentally influenced diseases. The research continues, but one message comes through clearly: when it comes to health, both our genes and our environments matter, and so do the intricate ways they talk to each other from the moment we're born until our final breath.