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Advancing Tools for Human Early Lifecourse Exposome Research and Translation

Periodic Reporting for period 2 - ATHLETE (Advancing Tools for Human Early Lifecourse Exposome Research and Translation)

Período documentado: 2021-07-01 hasta 2022-12-31

Through our environment we are exposed to a cocktail of harmful and beneficial influences on health. The human exposome encompasses this complexity by studying the totality of environmental exposures throughout life. It promotes a fundamental shift in how we study environmental impacts on health, by moving to a more holistic approach.
The early stages of life are particularly vulnerable to environmental hazards, with potential lifetime health consequences. This makes early life a relevant starting point for exposome studies and an important window for implementing actions to prevent disease.
ATHLETE (Advancing Tools for Human Early Lifecourse Exposome Research and Translation) aims to better understand and prevent health damage from numerous environmental hazards and their mixtures (chemical pollutants, urban environment, lifestyle, socio-economic factors), starting from the earliest stages of life. The project will develop an exposome toolbox that can be used by researchers, policymakers and other stakeholders to evaluate the health effects of a large number of environmental exposures and underpin the development of prevention strategies.
WP1 has 1) extended the existing LifeCycle infrastructure by adding exposome variables and new cohorts and building a new catalogue, and by installing the data access network across 18 cohorts; 2) completed data harmonisation in most new cohorts and completed harmonisation of new ATHLETE variables in others; data are uploaded on Opal/Armadillo servers; 3) started development of a plan to add the HELIX subcohort dataset to the infrastructure; 4) finished fieldwork in all 6 cohorts for the new HELIX follow-up (N=866), started or completed shipment of biological samples to labs; transferred data from HELIX cohorts to ISGlobal.
WP2 has finished method development needed to assess the chemical exposome both using targeted and untargeted approaches. The protocols and App developed to assess the personal/behavioural and external exposome have successfully been used in the fieldwork. Indicators to assess household income and degree of urbanisation have been derived. Socio-economic inequalities in the exposome pattern are observed from the earliest years of life. A mixture risk assessment of chemicals in food relevant for developmental neurotoxicity has been performed for 4 age groups.
WP3 has 1) developed statistical techniques and simulations to compare methodologies, and made software tools available; 2) developed tools and tutorials to conduct analysis using DataSHIELD; and 3) organized several courses and workshops on statistical analysis of exposome.
WP4 has 1) developed new protocols for molecular biomarker measurements; 2) developed interoperability protocols for omics data; 3) established new molecular signatures linked to exposure and child health; 4) conducted evaluation studies and developed tools for untargeted metabolomics in exposome studies; 5) systematically reviewed the evidence for health effects in children of developmental neurotoxicants and the molecular pathways (AOPs) that cause these effects; and 6) conducted experiments in cellular models to help explain the links between exposures, molecular biomarkers and health outcomes in children.
Since the beginning of the project WP5 and WP6 worked on 1) identifying already harmonized health outcomes and new health outcomes to be harmonized, 2) identifying and initiating the exposome-health outcome association studies across many ATHLETE cohorts, using the data infrastructure constructed in WP1, and 3) publishing first results of exposome-health associations using data from individual cohorts.
WP7 has co-produced and collected baseline and intervention data for the urban exposome study and piloted the chemical exposome study. A systematic review on interventions to improve the urban exposome has been published and a scoping review on interventions to alter the chemical exposome has been accepted for publications.
WP8 reviewed the agency reports to identify environmental factors (chemical and physical exposures) most likely to impact child health. Their level of evidence based on a weight of evidence (WoE) approach combining toxicological and human evidence was reported in the plausibility database that will be accessible online. The corresponding dose-response functions are being retrieved or estimated, for use in a health impact assessment estimation.
WP9 has set the ground for the project communication material, tools and channels used for the dissemination of research findings and insert key messages in policy debates and implementation.
WP1 has created an infrastructure that is assembling a large, harmonised, prospective exposome cohort to make exposome data FAIR; this infrastructure also makes federated data analysis possible. New data collection is adding prospective exposome data to the rich HELIX database with new measurements of exposures, omics, and health outcomes.
WP2 is developing and applying novel exposure science tools for complete and accurate assessment of the external, chemical, physical, behavioural, and social exposome, and provide harmonized exposure estimates to the ATHLETE cohorts. WP2 applies a complementary approach of targeted and untargeted chemical biomonitoring, personal and indoor monitoring, remote sensing and geospatial models, and questionnaires, as well as improved biosampling strategies. Novel tools from social science and toxicology are used to assess drivers and sources of the personal exposome, that will be highly relevant for development of policy recommendations.
WP3 is developing statistical and bioinformatics strategies to tackle the next set of analytical exposome challenges, including the evaluation of longitudinal exposome-health associations, the estimation of combined effects of exposures, causal structure models, integration of cross-omics data, and conducting exposome analyses in a non-disclosive way.
WP4 focuses on new biological pathways and approaches, such as the microbiome, placental epigenetics, composite measures for ageing and stress pathways and cross-omics risk prediction, in longitudinal datasets, which will push the integration of omics data into environmental health studies beyond the state-of-the-art. Our experimental models will provide complementary molecular validation of toxicological mechanisms, greatly amplifying our confidence in causal pathways.
The first exposome-health outcome association studies conducted or in progress in WP5 and WP6 provide additional support to highlight the role of early-life environment on child health. Until the endo of the project, results of WP 5 and 6 will contribute to further decipher the role of environment on child health from fetal life up to adolescence.
The development of acceptable and feasible interventions in WP7, to reduce personal exposures to the harmful effects of both the urban and the chemical exposome, will be important for the translation of exposome results into practical recommendations.
WP8 completed an evidence plausibility database regarding the hazards induced by the exposome on children health, which can be used to identify research gaps and conduct quantitative risk assessment studies. Further, WP8 reviewed the literature from epidemiological data on effects and dose-response relationships between the chemical and urban exposome and children’s health, as basis for further health impact assessment.
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