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Early-life exposure to perfluorinated alkyl substances modulates lipid metabolism in progression to celiac disease
medRxiv - Allergy and Immunology Pub Date : 2020-04-15 , DOI: 10.1101/2020.04.02.20051359
Lisanna Sinisalu , Partho Sen , Samira Salihović , Suvi M. Virtanen , Heikki Hyöty , Jorma Ilonen , Jorma Toppari , Riitta Veijola , Matej Orešič , Mikael Knip , Tuulia Hyötyläinen

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.

中文翻译:

生命早期暴露于全氟烷基物质可调节脂质代谢,进而发展为乳糜泻

目的乳糜泻(CD)是一种系统性免疫介导的疾病,在过去的几十年中,发达国家的发病率呈上升趋势,暗示除了麸质外,各种环境诱因也可能具有潜在的因果作用。本文中,我们采用全氟烷基物质(PFAS)的测定方法,并将结果与​​胆汁酸(BAs)和分子脂质的测定方法结合起来,目的是阐明在一系列前瞻性研究中,产前暴露对进展为CD的风险的影响。第一次接触面筋的儿童(出生时和3个月大时)。方法我们在1型糖尿病预测和预防(DIPP)研究(n = 17进展为CD,n = 16健康对照,HCs)中分析了76例出生时和3个月大时血浆样本中的PFAS,BAs和脂质组学概况。结果血浆PFAS水平与后来发展为该疾病的婴儿的CD诊断年龄呈显着负相关。BA和三酰甘油(TG)之间的关联显示,CD进展者在出生时已经存在不同的模式,表明这些婴儿中脂质的吸收不同。讨论PFAS暴露可能会调节脂质和BA的代谢,与HCs相比,在生命后期发展CD的婴儿的影响是不同的。结果表明此类婴儿更有效地摄取PFAS。在有遗传倾向的儿童中,产前和生命早期较高的PFAS暴露量可能会加速CD的发展。BA和三酰甘油(TG)之间的关联显示,CD进展者在出生时已经存在不同的模式,表明这些婴儿中脂质的吸收不同。讨论PFAS暴露可能会调节脂质和BA的代谢,与HCs相比,在生命后期发展CD的婴儿的影响是不同的。结果表明此类婴儿更有效地摄取PFAS。在有遗传倾向的儿童中,产前和生命早期较高的PFAS暴露量可能会加速CD的发展。BA和三酰甘油(TG)之间的关联显示,CD进展者在出生时已经存在不同的模式,表明这些婴儿中脂质的吸收不同。讨论PFAS暴露可能会调节脂质和BA的代谢,与HCs相比,在生命后期发展CD的婴儿的影响是不同的。结果表明此类婴儿更有效地摄取PFAS。在有遗传倾向的儿童中,产前和生命早期较高的PFAS暴露量可能会加速CD的发展。
更新日期:2020-04-15
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