An exposome connectivity paradigm for the mechanistic assessment of the effects of prenatal and early life exposure to metals on neurodevelopment

The exposome paradigm through an integrated approach to investigating the impact of perinatal exposure to metals on child neurodevelopment in two cohorts carried out in Slovenia (PHIME cohort) and Greece (HERACLES cohort) respectively, is presented herein. Heavy metals are well-known neurotoxicants...

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Main Authors: Ourania Anesti, Nafsika Papaioannou, Catherine Gabriel, Achilleas Karakoltzidis, Vazha Dzhedzheia, Ioannis Petridis, Antonios Stratidakis, Mike Dickinson, Milena Horvat, Janja Snoj Tratnik, Aristidis Tsatsakis, Spyros Karakitsios, Dimosthenis A. Sarigiannis
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Public Health
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fpubh.2022.871218/full
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author Ourania Anesti
Ourania Anesti
Nafsika Papaioannou
Nafsika Papaioannou
Catherine Gabriel
Catherine Gabriel
Achilleas Karakoltzidis
Achilleas Karakoltzidis
Vazha Dzhedzheia
Vazha Dzhedzheia
Ioannis Petridis
Ioannis Petridis
Antonios Stratidakis
Mike Dickinson
Milena Horvat
Janja Snoj Tratnik
Aristidis Tsatsakis
Spyros Karakitsios
Spyros Karakitsios
Dimosthenis A. Sarigiannis
Dimosthenis A. Sarigiannis
Dimosthenis A. Sarigiannis
author_facet Ourania Anesti
Ourania Anesti
Nafsika Papaioannou
Nafsika Papaioannou
Catherine Gabriel
Catherine Gabriel
Achilleas Karakoltzidis
Achilleas Karakoltzidis
Vazha Dzhedzheia
Vazha Dzhedzheia
Ioannis Petridis
Ioannis Petridis
Antonios Stratidakis
Mike Dickinson
Milena Horvat
Janja Snoj Tratnik
Aristidis Tsatsakis
Spyros Karakitsios
Spyros Karakitsios
Dimosthenis A. Sarigiannis
Dimosthenis A. Sarigiannis
Dimosthenis A. Sarigiannis
author_sort Ourania Anesti
collection DOAJ
description The exposome paradigm through an integrated approach to investigating the impact of perinatal exposure to metals on child neurodevelopment in two cohorts carried out in Slovenia (PHIME cohort) and Greece (HERACLES cohort) respectively, is presented herein. Heavy metals are well-known neurotoxicants with well-established links to impaired neurodevelopment. The links between in utero and early-life exposure to metals, metabolic pathway dysregulation, and neurodevelopmental disorders were drawn through urinary and plasma untargeted metabolomics analysis, followed by the combined application of in silico and biostatistical methods. Heavy metal prenatal and postnatal exposure was evaluated, including parameters indirectly related to exposure and health adversities, such as sociodemographic and anthropometric parameters and dietary factors. The primary outcome of the study was that the identified perturbations related to the TCA cycle are mainly associated with impaired mitochondrial respiration, which is detrimental to cellular homeostasis and functionality; this is further potentiated by the capacity of heavy metals to induce oxidative stress. Insufficient production of energy from the mitochondria during the perinatal period is associated with developmental disorders in children. The HERACLES cohort included more detailed data regarding diet and sociodemographic status of the studied population, allowing the identification of a broader spectrum of effect modifiers, such as the beneficial role of a diet rich in antioxidants such as lycopene and ω-3 fatty acids, the negative effect the consumption of food items such as pork and chicken meat has or the multiple impacts of fish consumption. Beyond diet, several other factors have been proven influential for child neurodevelopment, such as the proximity to pollution sources (e.g., waste treatment site) and the broader living environment, including socioeconomic and demographic characteristics. Overall, our results demonstrate the utility of exposome-wide association studies (EWAS) toward understanding the relationships among the multiple factors that determine human exposure and the underlying biology, reflected as omics markers of effect on neurodevelopment during childhood.
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spelling doaj.art-2b10ec52dbec43e7b8d4a5c66ea3c4c22023-01-10T15:32:53ZengFrontiers Media S.A.Frontiers in Public Health2296-25652023-01-011010.3389/fpubh.2022.871218871218An exposome connectivity paradigm for the mechanistic assessment of the effects of prenatal and early life exposure to metals on neurodevelopmentOurania Anesti0Ourania Anesti1Nafsika Papaioannou2Nafsika Papaioannou3Catherine Gabriel4Catherine Gabriel5Achilleas Karakoltzidis6Achilleas Karakoltzidis7Vazha Dzhedzheia8Vazha Dzhedzheia9Ioannis Petridis10Ioannis Petridis11Antonios Stratidakis12Mike Dickinson13Milena Horvat14Janja Snoj Tratnik15Aristidis Tsatsakis16Spyros Karakitsios17Spyros Karakitsios18Dimosthenis A. Sarigiannis19Dimosthenis A. Sarigiannis20Dimosthenis A. Sarigiannis21HERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, Thessaloniki, GreeceCentre of Toxicology Science and Research, School of Medicine, University of Crete, Heraklion, GreeceHERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, Thessaloniki, GreeceEnvironmental Engineering Laboratory, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, GreeceHERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, Thessaloniki, GreeceEnvironmental Engineering Laboratory, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, GreeceHERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, Thessaloniki, GreeceEnvironmental Engineering Laboratory, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, GreeceHERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, Thessaloniki, GreeceEnvironmental Engineering Laboratory, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, GreeceHERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, Thessaloniki, GreeceEnvironmental Engineering Laboratory, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, GreeceScience, Technology, and Society Department, Istituto Universitario di Studi Superiori (IUSS), University School for Advanced Study, Pavia, ItalyFera Science Ltd., York, United KingdomDepartment of Environmental Sciences, Josef Stefan Institute, Ljubljana, SloveniaDepartment of Environmental Sciences, Josef Stefan Institute, Ljubljana, SloveniaCentre of Toxicology Science and Research, School of Medicine, University of Crete, Heraklion, GreeceHERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, Thessaloniki, GreeceEnvironmental Engineering Laboratory, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, GreeceHERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, Thessaloniki, GreeceCentre of Toxicology Science and Research, School of Medicine, University of Crete, Heraklion, GreeceEnvironmental Engineering Laboratory, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, GreeceThe exposome paradigm through an integrated approach to investigating the impact of perinatal exposure to metals on child neurodevelopment in two cohorts carried out in Slovenia (PHIME cohort) and Greece (HERACLES cohort) respectively, is presented herein. Heavy metals are well-known neurotoxicants with well-established links to impaired neurodevelopment. The links between in utero and early-life exposure to metals, metabolic pathway dysregulation, and neurodevelopmental disorders were drawn through urinary and plasma untargeted metabolomics analysis, followed by the combined application of in silico and biostatistical methods. Heavy metal prenatal and postnatal exposure was evaluated, including parameters indirectly related to exposure and health adversities, such as sociodemographic and anthropometric parameters and dietary factors. The primary outcome of the study was that the identified perturbations related to the TCA cycle are mainly associated with impaired mitochondrial respiration, which is detrimental to cellular homeostasis and functionality; this is further potentiated by the capacity of heavy metals to induce oxidative stress. Insufficient production of energy from the mitochondria during the perinatal period is associated with developmental disorders in children. The HERACLES cohort included more detailed data regarding diet and sociodemographic status of the studied population, allowing the identification of a broader spectrum of effect modifiers, such as the beneficial role of a diet rich in antioxidants such as lycopene and ω-3 fatty acids, the negative effect the consumption of food items such as pork and chicken meat has or the multiple impacts of fish consumption. Beyond diet, several other factors have been proven influential for child neurodevelopment, such as the proximity to pollution sources (e.g., waste treatment site) and the broader living environment, including socioeconomic and demographic characteristics. Overall, our results demonstrate the utility of exposome-wide association studies (EWAS) toward understanding the relationships among the multiple factors that determine human exposure and the underlying biology, reflected as omics markers of effect on neurodevelopment during childhood.https://www.frontiersin.org/articles/10.3389/fpubh.2022.871218/fullexposomeearly life exposuremetabolomicsmetalsneurodevelopmental disorders
spellingShingle Ourania Anesti
Ourania Anesti
Nafsika Papaioannou
Nafsika Papaioannou
Catherine Gabriel
Catherine Gabriel
Achilleas Karakoltzidis
Achilleas Karakoltzidis
Vazha Dzhedzheia
Vazha Dzhedzheia
Ioannis Petridis
Ioannis Petridis
Antonios Stratidakis
Mike Dickinson
Milena Horvat
Janja Snoj Tratnik
Aristidis Tsatsakis
Spyros Karakitsios
Spyros Karakitsios
Dimosthenis A. Sarigiannis
Dimosthenis A. Sarigiannis
Dimosthenis A. Sarigiannis
An exposome connectivity paradigm for the mechanistic assessment of the effects of prenatal and early life exposure to metals on neurodevelopment
Frontiers in Public Health
exposome
early life exposure
metabolomics
metals
neurodevelopmental disorders
title An exposome connectivity paradigm for the mechanistic assessment of the effects of prenatal and early life exposure to metals on neurodevelopment
title_full An exposome connectivity paradigm for the mechanistic assessment of the effects of prenatal and early life exposure to metals on neurodevelopment
title_fullStr An exposome connectivity paradigm for the mechanistic assessment of the effects of prenatal and early life exposure to metals on neurodevelopment
title_full_unstemmed An exposome connectivity paradigm for the mechanistic assessment of the effects of prenatal and early life exposure to metals on neurodevelopment
title_short An exposome connectivity paradigm for the mechanistic assessment of the effects of prenatal and early life exposure to metals on neurodevelopment
title_sort exposome connectivity paradigm for the mechanistic assessment of the effects of prenatal and early life exposure to metals on neurodevelopment
topic exposome
early life exposure
metabolomics
metals
neurodevelopmental disorders
url https://www.frontiersin.org/articles/10.3389/fpubh.2022.871218/full
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