Early-life exposome and health-related immune signatures in childhood
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
Early-life environmental exposures are suspected to modify important immune processes related to child health. Yet, no study has investigated immunotoxicity in relation to the exposome and multiple health domains simultaneously.
Methods
Among 845 children (median age 8) from six European birth cohorts included in the Human Early-Life Exposome (HELIX) project, we identified immune signatures of a health score covering cardiometabolic, respiratory/allergic and neurodevelopmental health in children. Those signatures were identified from blood samples in three biological layers (white blood cell (WBC) composition, plasma proteins concentrations, DNA methylation of WBCs) using an advanced factorial analysis supervised on the child health score. Second, we estimated the association between the identified signatures and 91 pre- and postnatal environmental exposures.
Results
Three key immune signatures were associated with a better health score in children: a first protein signature characterizing a low inflammatory profile (R2 = 17 %), a second protein signature characterizing a low inflammatory profile with balanced antiviral Th response (R2 = 2 %), and a WBC signature characterizing an immuno-regulatory and naïve profile (R2 = 2 %). In childhood, less exposure to indoor air pollutants, proximity to blue spaces and public transport, healthy dietary habits and higher social capital were associated with the three immune signatures related to a better health score (regression p-values < 0.05). One signature was identified from DNA methylation, but was not significantly associated with the health score nor with the exposome.
Conclusions
These findings highlight the influence of early-life environmental exposures on key inflammatory processes associated with the cardiometabolic, respiratory and neurodevelopmental health of children.
Early-life environmental exposures are suspected to modify important immune processes related to child health. Yet, no study has investigated immunotoxicity in relation to the exposome and multiple health domains simultaneously.
Methods
Among 845 children (median age 8) from six European birth cohorts included in the Human Early-Life Exposome (HELIX) project, we identified immune signatures of a health score covering cardiometabolic, respiratory/allergic and neurodevelopmental health in children. Those signatures were identified from blood samples in three biological layers (white blood cell (WBC) composition, plasma proteins concentrations, DNA methylation of WBCs) using an advanced factorial analysis supervised on the child health score. Second, we estimated the association between the identified signatures and 91 pre- and postnatal environmental exposures.
Results
Three key immune signatures were associated with a better health score in children: a first protein signature characterizing a low inflammatory profile (R2 = 17 %), a second protein signature characterizing a low inflammatory profile with balanced antiviral Th response (R2 = 2 %), and a WBC signature characterizing an immuno-regulatory and naïve profile (R2 = 2 %). In childhood, less exposure to indoor air pollutants, proximity to blue spaces and public transport, healthy dietary habits and higher social capital were associated with the three immune signatures related to a better health score (regression p-values < 0.05). One signature was identified from DNA methylation, but was not significantly associated with the health score nor with the exposome.
Conclusions
These findings highlight the influence of early-life environmental exposures on key inflammatory processes associated with the cardiometabolic, respiratory and neurodevelopmental health of children.
Date Issued
2025-08-01
Date Acceptance
2025-07-04
Citation
Environment International, 2025, 202
ISSN
0160-4120
Publisher
Elsevier BV
Journal / Book Title
Environment International
Volume
202
Copyright Statement
© 2025 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40651279
PII: S0160-4120(25)00419-2
Subjects
Exposome
General health status
Immunotoxicity
Multi-Omics
Outcome-wide
Humans
Child
Exposome
Environmental Exposure
Female
Male
DNA Methylation
Child, Preschool
Child Health
Infant
Publication Status
Published
Coverage Spatial
Netherlands
Article Number
109668
Date Publish Online
2025-07-05