Early-life exposure to perfluorinated alkyl substances modulates lipid metabolism in progression to celiac disease

Lisanna Sinisalu,Partho Sen,Samira Salihović,Suvi M Virtanen,Heikki Hyöty,Jorma Ilonen,Jorma Toppari,Riitta Veijola,Matej Orešič,Mikael Knip,Tuulia Hyötyläinen

doi:10.1016/j.envres.2020.109864

Abstract

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). Here we analyzed PFAS, BAs and lipidomic profiles in 66 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). 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. In conclusion, 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.

Highlights

Celiac disease (CD) is a systemic immune-mediated disorder, which is triggered by gluten and other prolamins in genetically susceptible individuals (Caio et al, 2019)
We investigated the impact of early-life exposure to per fluorinated alkyl substances (PFAS) in chil dren who progressed to clinical CD during their follow-up, and compared the exposures to those observed in children who remained healthy during the follow-up
The current study suggests that the changes in TG metabolism are related to alteration in bile acids (BAs) metabolism, and that early-life exposure to PFAS may contribute to these changes

Summary

Introduction

Celiac disease (CD) is a systemic immune-mediated disorder, which is triggered by gluten and other prolamins in genetically susceptible individuals (Caio et al, 2019). The hygiene hypothesis, stating that a decrease of the infectious burden is associated with the rise of allergic and autoimmune diseases, has been proposed in CD because CD has shown to be more common in developed countries (Ol en et al, 2012; Whyte et al, 2014; Zingone et al, 2015) Another possible explanation for varying incidence in different populations implicates the role of different infant feeding patterns (including the amount and timing of gluten introduction) in families with low socioeconomic status (Zingone et al, 2015). We have recently identified systematic differences in plasma lipid profiles between children who later pro gressed to clinical CD during the follow-up, when compared to children who remained healthy (Sen et al, 2019) These differences were observed prior to the first introduction of gluten in the diet and before the first signs of CD-associated autoimmunity. Similar results were recently reported in an Italian cohort study (Auricchio et al, 2019)

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