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

Amine, Ines; Anguita Ruiz, Augusto; Basagaña Flores, Xavier; Bustamante Pineda, Mariona; Borràs, Eva; Cirach, Marta; Dobaño, Carlota; García Aymerich, Judith; González, Juan Ramón; Júlvez Calvo, Jordi; López Vicente, Mònica, 1988-; Moncunill, Gemma; Nieuwenhuijsen, Mark J.; Sabidó Aguadé, Eduard, 1981-; Vrijheid, Martine; Maitre, Léa

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

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dc.contributor.author Amine, Ines
dc.contributor.author Anguita Ruiz, Augusto
dc.contributor.author Basagaña Flores, Xavier
dc.contributor.author Bustamante Pineda, Mariona
dc.contributor.author Borràs, Eva
dc.contributor.author Cirach, Marta
dc.contributor.author Dobaño, Carlota
dc.contributor.author García Aymerich, Judith
dc.contributor.author González, Juan Ramón
dc.contributor.author Júlvez Calvo, Jordi
dc.contributor.author López Vicente, Mònica, 1988-
dc.contributor.author Moncunill, Gemma
dc.contributor.author Nieuwenhuijsen, Mark J.
dc.contributor.author Sabidó Aguadé, Eduard, 1981-
dc.contributor.author Vrijheid, Martine
dc.contributor.author Maitre, Léa
dc.date.accessioned 2025-09-15T06:19:11Z
dc.date.available 2025-09-15T06:19:11Z
dc.date.issued 2025
dc.description.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.
dc.description.sponsorship The study received funding from the European Community’s Seventh Framework Programme (FP7/2007–206) (grant agreement no 308,333 − HELIX project) and the H2020-EU.3.1.2. − Preventing Disease Programme (grant agreement no 874,583 − ATHLETE project). Born in Bradford receives funding from by a joint grant from the UK Medical Research Council (MRC) and UK Economic and Social Science Research Council (ESRC) [MR/N024391/1]; the British Heart Foundation [CS/16/4/32482]; a Wellcome Infrastructure Grant [WT101597MA]; the National Institute for Health Research under its Applied Research Collaboration for Yorkshire and Humber [NIHR200166]; and was supported by UK Research and Innovation for the Healthy Urban Places consortium (grant reference MR/Y022785/1) as part of Population Health Improvement UK (PHI-UK), a national research network which works to transform health and reduce inequalities through change at the population level. The views expressed are those of the author(s), and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Data collection at Infancia y Medio Ambiente (INMA) was supported by grants from the Instituto de Salud Carlos III, Centro de Investigacion Biomedica en Red Epidemiologia y Salud Publica, and the Generalitat de Catalunya-CIRIT. The Kaunas cohort (KANC) was supported by grant 6–04-2014_31V-66 and on September 13, 2015, by No. 31 V-77, from the Lithuanian Agency for Science Innovation and Technology. A full list of support for the Etude des Determinants Pre et Postnatals du Developpement et de la Sante de l’Enfant (EDEN) cohort is found in Heude B et al. Cohort profile: the EDEN mother–child cohort on the prenatal and early postnatal determinants of child health and development. Int J Epidemiol. 2016;45(2):353–363. The Norwegian Mother and Child Cohort Study (MoBa) is supported by the Norwegian Ministry of Health and the Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), and NIH/NINDS (grant no.1 UO1 NS 047537–01 and grant no.2 UO1 NS 047537-06A1). The RHEA Mother Child Cohort was supported by European projects and the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children, Heraklion, Crete, Greece: 2011–2014; “Rhea Plus”: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–2015). Additionally, ISGlobal acknowledges support from the “Centro de Excelencia Severo Ochoa 2019–2023” Program 2018–000806-S from the Spanish Ministry of Science and Innovation, and from the Generalitat de Catalunya through the Centres de Recerca de Catalunya (CERCA) Program.
dc.format.mimetype application/pdf
dc.identifier.citation Amine I, Anguita-Ruiz A, Guillien A, Basagaña X, Bustamante M, Borràs E, et al. Early-life exposome and health-related immune signatures in childhood. Environ Int. 2025 Aug;202:109668. DOI: 10.1016/j.envint.2025.109668
dc.identifier.doi http://dx.doi.org/10.1016/j.envint.2025.109668
dc.identifier.issn 0160-4120
dc.identifier.uri http://hdl.handle.net/10230/71191
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Environ Int. 2025 Aug;202:109668
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/308333
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/874583
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword Exposome
dc.subject.keyword General health status
dc.subject.keyword Immunotoxicity
dc.subject.keyword Multi-Omics
dc.subject.keyword Outcome-wide
dc.title Early-life exposome and health-related immune signatures in childhood
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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