Early-life exposome and health-related immune signatures in childhood

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.