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

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 Europea...

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Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/71191
Acceso en línea:http://hdl.handle.net/10230/71191
http://dx.doi.org/10.1016/j.envint.2025.109668
Access Level:acceso abierto
Palabra clave:Exposome
General health status
Immunotoxicity
Multi-Omics
Outcome-wide
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network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Early-life exposome and health-related immune signatures in childhood
title Early-life exposome and health-related immune signatures in childhood
spellingShingle Early-life exposome and health-related immune signatures in childhood
Amine, Ines
Exposome
General health status
Immunotoxicity
Multi-Omics
Outcome-wide
title_short Early-life exposome and health-related immune signatures in childhood
title_full Early-life exposome and health-related immune signatures in childhood
title_fullStr Early-life exposome and health-related immune signatures in childhood
title_full_unstemmed Early-life exposome and health-related immune signatures in childhood
title_sort Early-life exposome and health-related immune signatures in childhood
dc.creator.none.fl_str_mv 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
author Amine, Ines
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Exposome
General health status
Immunotoxicity
Multi-Omics
Outcome-wide
topic Exposome
General health status
Immunotoxicity
Multi-Omics
Outcome-wide
description 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.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/71191
http://dx.doi.org/10.1016/j.envint.2025.109668
url http://hdl.handle.net/10230/71191
http://dx.doi.org/10.1016/j.envint.2025.109668
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Environ Int. 2025 Aug;202:109668
info:eu-repo/grantAgreement/EC/FP7/308333
info:eu-repo/grantAgreement/EC/H2020/874583
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
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spelling Early-life exposome and health-related immune signatures in childhoodAmine, InesAnguita Ruiz, AugustoBasagaña Flores, XavierBustamante Pineda, MarionaBorràs, EvaCirach, MartaDobaño, CarlotaGarcía Aymerich, JudithGonzález, Juan RamónJúlvez Calvo, JordiLópez Vicente, Mònica, 1988-Moncunill, GemmaNieuwenhuijsen, Mark J.Sabidó Aguadé, Eduard, 1981-Vrijheid, MartineMaitre, LéaExposomeGeneral health statusImmunotoxicityMulti-OmicsOutcome-wideBackground: 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.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.Elsevier202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/71191http://dx.doi.org/10.1016/j.envint.2025.109668reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésEnviron Int. 2025 Aug;202:109668info:eu-repo/grantAgreement/EC/FP7/308333info:eu-repo/grantAgreement/EC/H2020/874583© 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/).http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/711912026-06-12T07:21:37Z
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