Associations between pre- and post-natal exposure to phthalate and DINCH metabolites and gut microbiota in one-year old children
2024
Davias, Aline | Lyon-Caen, Sarah | Rolland, Matthieu | Iszatt, Nina | Thomsen, Cathrine | Sabaredzovic, Azemira | Sakhi, Amrit, Kaur | Monot, Celine | Rayah, Yamina | Ilhan, Zehra, Esra | Philippat, Claire | Eggesbø, Merete | Lepage, Patricia | Slama, Rémy | Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB) ; Centre Hospitalier Universitaire [CHU Grenoble] (CHUGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA) | Norwegian Institute of Public Health [Oslo] (NIPH) | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Département Alimentation Humaine - INRAE (ALIM-H) ; Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Norwegian University of Life Sciences (NMBU) | NTNU Acoustics Research Center ; Norwegian University of Science and Technology [Trondheim] (NTNU) ; Norwegian University of Science and Technology (NTNU)-Norwegian University of Science and Technology (NTNU) | Institut de biologie de l'ENS Paris (IBENS) ; Département de Biologie - ENS-PSL (IBENS) ; École normale supérieure - Paris (ENS-PSL) ; Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL) ; Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) | ANR-17-CE34-0013,GUMME,Microbiote intestinal dans l'enfance et expositions environnementales maternelles(2017) | ANR-12-PDOC-0029,PAPER,Grossesse, pollution atmospherique, epigenetique, et sante respiratoire(2012) | ANR-14-CE21-0007,SHALCOH,Expositions prénatales aux phénols et santé de l'enfant : analyse longitudinale(2014) | ANR-15-IDEX-0005,ANR-15- IDEX5,ANR-15- IDEX5 | ANR-18-CE36-0005,ETAPE,Exposition prénatale au tabac et à la pollution atmosphérique et effets sur la santé respiratoire et le neurodévelopment de l'enfant: rôle de la méthylation placentaire(2018) | ANR-19-CE36-0003,EDeN,Exposition précoces aux perturbateurs endocriniens et neurodéveloppement de l'enfant : le rôle de l'axe hypothalamo-hypophysaire(2019) | ANR-21-CE34-0022,MEMORI,Exposition maternelle à un mélange de polluants organiques: marques épigénétiques placentaires et évaluation des risques pour la santé de la descendance(2021) | ANR-22-CE36-0018,ORANDANI,Les retardateurs de flamme organophosphorés affectent-ils le neurodéveloppement ? Investigation par neuroimagerie(2022) | European Project: 311765,EC:FP7:ERC,ERC-2012-StG_20111109,E-DOHAD(2013) | European Project: 308333,EC:FP7:ENV,FP7-ENV-2012-two-stage,HELIX(2013) | European Project: 874583,H2020,H2020-EU.3.1.2.,ATHLETE(2020)
International audience
Show more [+] Less [-]English. The gut microbiota is a collection of symbiotic microorganisms in the gastrointestinal tract. Its sensitivity to chemicals with widespread exposure, such as phthalates, is little known. We aimed to investigate the impact of perinatal exposure to phthalates on the infant gut microbiota at 12 months of age. Within SEPAGES cohort (Suivi de l'Exposition à la Pollution Atmosphérique durant la Grossesse et Effet sur la Santé), we assessed 13 phthalate metabolites and 2 di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) metabolites in repeated urine samples collected in pregnant women and their offspring. We obtained stool samples from 356 children at 12 months of age and sequenced the V3-V4 region of the 16S rRNA gene, allowing gut bacterial profiling. We used single-chemical (linear regressions) and mixture (BKMR, Bayesian Kernel Machine Regression) models to examine associations of phthalates and DINCH metabolites, with gut microbiota indices of α-diversity (specific richness and Shannon diversity) and the relative abundances of the most abundant microbiota phyla and genera. After correction for multiple testing, di(2-ethylhexyl) phthalate (ΣDEHP), diethyl phthalate (DEP) and bis(2-propylheptyl) phthalate (DPHP) metabolites 12-month urinary concentrations were associated with higher Shannon α-diversity of the child gut microbiota in single-chemical models. The multiple-chemical model (BKMR) suggested higher α-diversity with exposure to the phthalate mixture at 12 months, driven by the same phthalates. There were no associations between phthalate and DINCH exposure biomarkers at other time points and α-diversity after correction for multiple testing. ΣDEHP metabolites concentration at 12 months was associated with higher Coprococcus genus. Finally, ΣDEHP exposure at 12 months tended to be associated with higher phylum Firmicutes, an association not maintained after correction for multiple testing. Infancy exposure to phthalate might disrupt children's gut microbiota. The observed associations were cross-sectional, so that reverse causality cannot be excluded.
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