Early-life exposure to perfluorinated alkyl substances modulates lipid metabolism in progression to celiac disease
Year: 2020
Type: article
Abstract: OBJECTIVES Celiac disease (CD) is a systemic immune-mediated disorder with increased frequency in the developed countries over the last decades implicating the potential causal role of various environmental triggers in addition to gluten. Herein, we apply determination of perfluorinated alkyl substances (PFAS) and combine the results with the determination of bile acids (BAs) and molecular lipids, with the aim to elucidate the impact of prenatal exposure on risk of progression to CD in a prospective series of children prior the first exposure to gluten (at birth and at 3 months of age). METHODS We analyzed PFAS, BAs and lipidomic profiles in 76 plasma samples at birth and at 3 months of age in the Type 1 Diabetes Prediction and Prevention (DIPP) study (n=17 progressors to CD, n=16 healthy controls, HCs). RESULTS Plasma PFAS levels showed a significant inverse association with the age of CD diagnosis in infants who later progressed to the disease. Associations between BAs and triacylglycerols (TGs) showed different patterns already at birth in CD progressors, indicative of different absorption of lipids in these infants. DISCUSSION PFAS exposure may modulate lipid and BA metabolism, and the impact is different in the infants who develop CD later in life, in comparison to HCs. The results indicate more efficient uptake of PFAS in such infants. Higher PFAS exposure during prenatal and early life may accelerate the progression to CD in the genetically predisposed children. Study Highlights WHAT IS KNOWN Several observational studies have implicated a role of early life environmental triggers other than gluten in the development of CD. This is supported by the findings showing dysregulation of lipids already prior to the first introduction of gluten. WHAT IS NEW HERE We show that prenatal exposure to perfluorinated compounds is associated with changes in the lipid metabolism, most likely through the bile acids, and that a high exposure during prenatal and early life may accelerate the progression to CD in the genetically predisposed children. TRANSLATIONAL IMPACT Exposure to environmental chemicals may impact the rate of progression to CD and should be assessed as a potential risk factor of CD in larger clinical cohort settings.
Source: Environmental Research
Institutions: Örebro University, Åbo Akademi University, University of Turku, Tampere University, Finnish Institute for Health and Welfare, Tampere University Hospital, University of Tampere, Pirkanmaa Hospital District, Fimlab (Finland), Turku University Hospital, Oulu University Hospital, Karolinska Institutet, University of Oulu, University of Helsinki, Helsinki University Hospital, Helsinki Children's Hospital
Language: English
Subfield: Environmental Chemistry
Field: Environmental Science
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,550
Funders: Juvenile Diabetes Research Foundation United States of America, European Commission, Svenska Forskningsrådet Formas, Academy of Finland, Novo Nordisk, Vetenskapsrådet, Novo Nordisk Fonden, Fonds Spéciaux de Recherche, Directorate-General for Research and Innovation, Terveyden Tutkimuksen Toimikunta
Awards: G1225600041, G1410251319, G1969949363, G288617984, G3179115814, G4434344473, G4874821757, Health Consequences of Environmental Exposures in Early Life, G7167531271, G7546696832, G7643706808, G785763344, G8041825619, G8386306301, G8682467043, Metabolomics and mixture toxicology in the characterization of human exposome
OpenAlex ID: W3038315661