A groundbreaking new study spearheaded by the Barcelona Institute for Global Health (ISGlobal), in collaboration with INSERM and Université Grenoble Alpes, has illuminated the profound impact of early-life environmental exposures on children’s immune regulation and long-term health. Published in the prestigious journal Environment International, this extensive research draws from the diverse Human Early Life Exposome (HELIX) cohort, revealing how multifaceted exposures—from the quality of indoor air to social fabric—can shape the immune system’s trajectory and influence susceptibility to chronic diseases later in life.
At the heart of this study is the concept of the exposome—the comprehensive total of environmental exposures that an individual encounters from conception onward. While previous research has typically isolated single environmental factors, this new investigation takes a holistic approach, examining the interplay of 91 different exposures clustered into thirteen distinct families. These categories range from outdoor air pollutants and proximity to green and blue natural spaces, to indoor chemical agents, household air quality, lifestyle elements like diet and tobacco exposure, and complex socioeconomic indicators including parental education and community support networks.
Central to the research is the immune system’s response during critical windows of early development, a period when regulation of inflammation has far-reaching implications for a child’s cardiometabolic, respiratory, and neurodevelopmental health. Chronic inflammation is a well-recognized pathway in the etiology of major health burdens such as obesity, diabetes, asthma, and neurodevelopmental disorders. Understanding how the exposome influences immune system programming could pave the way for innovative prevention strategies targeting inflammation at its roots.
The HELIX cohort, encompassing 845 children from six European countries including the United Kingdom, France, Spain, Lithuania, Norway, and Greece, provided a rich, population-based dataset. This geographically diverse sample allowed researchers to capture a wide spectrum of environmental variability. Notably, pre- and postnatal exposures were meticulously assessed, affording insights into how the intrauterine and early childhood environments collectively shape immune ontogeny.
To dissect the complex interactions between exposures and immune function, the researchers employed a multi-omics approach combining three biological layers from blood samples: white blood cell composition, plasma protein concentrations related to immune signaling, and genome-wide DNA methylation patterns of white blood cells. This triad offered a powerful lens through which to monitor immune signatures, encompassing both the cellular components and epigenetic influences that govern inflammation and immune regulation.
The data analysis involved sophisticated statistical modeling, notably Regularized Generalized Canonical Correlation Analysis (RGCCA), an advanced algorithm adept at integrating high-dimensional multi-omics and exposome datasets. By aligning immune system profiles with composite health scores—incorporating respiratory function, metabolic health, and cognitive outcomes—the team delineated immune “signatures” that correlate with better overall health trajectories in children.
Most notably, the study identified three distinct immune profiles that were robustly associated with improved health outcomes. Two of these signatures, characterized by reduced levels of inflammatory plasma proteins, suggest a systemic attenuation of low-grade chronic inflammation. The third immune pattern reflected a more equilibrated white blood cell profile, indicative of finely tuned immune regulation rather than immune hyperactivation or dysregulation.
What distinguishes this research is its elucidation of specific environmental determinants linked to these favorable immune signatures. Better indoor air quality emerged as a pivotal factor—a finding particularly relevant given children’s prolonged exposure to indoor environments. Proximity to blue spaces, such as lakes, rivers, and coastal areas, was also strongly associated with healthier immune profiles, underscoring the salutogenic effects of natural water bodies on physiological stress reduction and immune modulation.
Dietary patterns exhibiting higher nutritional quality and adherence to healthy eating guidelines correlated with the beneficial immune patterns, reinforcing the role of nutrition in immune development. Furthermore, higher levels of social capital—encompassing family cohesion, community engagement, and social support networks—were linked to the regulation of immune function. These social determinants likely buffer stress and modulate neuroimmune pathways, contributing to reduced inflammatory activation.
The implications of these findings are profound. They highlight modifiable environmental factors that can be targeted through public health policies and community interventions to foster healthier immune development in children, potentially curbing the rise of chronic diseases rooted in childhood inflammation. The researchers advocate for integrated strategies focusing on indoor environmental improvements, preservation of natural spaces, promotion of nutritious diets, and bolstering of social support systems.
Lead author Ines Amine emphasized the complexity and novelty of integrating multi-omics immunological data with a broad spectrum of environmental exposures during early life. This systems biology approach uncovers mechanisms underlying the exposome’s influence on immunity, providing a blueprint for future research and policy action. Co-author Léa Maitre, coordinator of the Exposome Hub at ISGlobal, articulated the clinical significance of mitigating immunotoxicity through environmental interventions, especially given the rising public health burden of non-communicable diseases with inflammatory etiologies.
This study represents a landmark step in exposome research, situating immune regulation as a critical nexus between environment and health. It further exemplifies the power of collaborative international research consortia and cutting-edge data analytics in unraveling the complex determinants of pediatric health. The insights garnered herald new avenues for personalized and population-level preventive strategies, emphasizing the environment as a pivotal player in lifelong health trajectories.
In conclusion, by elucidating how quality of indoor air, closeness to natural spaces, dietary habits, and social fabric collectively influence immune development and inflammation regulation, this investigation calls for transformative investments in holistic environmental and social infrastructures. Such integrative approaches hold promise for diminishing the burden of chronic inflammatory diseases from childhood onward, ultimately fostering resilient and healthier future generations.
Subject of Research: People
Article Title: Early-life exposome and health-related immune signatures in childhood
References:
Amine, I., Anguita-Ruiz, A., Guillien, A., Basagaña, X., Bustamante, M., Borràs, E., Cirach, M., Dedele, A., Dobaño, C., Garcia-Aymerich, J., Granum, B., Grazuleviciene, R., González, J. R., Julvez, J., Keun, H., López-Vicente, M., McEachan, R., Moncunill, G., Nieuwenhuijsen, M., … Maitre, L. (2025). Early-life exposome and health-related immune signatures in childhood. Environment International, 202(109668), 109668. DOI: 10.1016/j.envint.2025.109668
Keywords:
Epigenetics, Immune system, Child welfare, Children
