关键词: Coeliac disease Exposome Gluten Gluten immunogenic peptides

Mesh : Humans Female Pregnancy Celiac Disease / immunology Glutens Adult Amniotic Fluid / chemistry metabolism Exposome Peptides Immunoassay / methods Gastric Inhibitory Polypeptide Fetus

来  源:   DOI:10.1186/s12916-024-03495-9   PDF(Pubmed)

Abstract:
BACKGROUND: The increasing incidence of coeliac disease is leading to a growing interest in active search for associated factors, even the intrauterine and early life. The exposome approach to disease encompasses a life course perspective from conception onwards has recently been highlighted. Knowledge of early exposure to gluten immunogenic peptides (GIP) in utero could challenge the chronology of early prenatal tolerance or inflammation, rather than after the infant\'s solid diet after birth.
METHODS: We developed an accurate and specific immunoassay to detect GIP in amniotic fluid (AF) and studied their accumulates, excretion dynamics and foetal exposure resulting from AF swallowing. One hundred twenty-five pregnant women with different gluten diets and gestational ages were recruited.
RESULTS: GIP were detectable in AF from at least the 16th gestational week in gluten-consuming women. Although no significant differences in GIP levels were observed during gestation, amniotic GIP late pregnancy was not altered by maternal fasting, suggesting closed-loop entailing foetal swallowing of GIP-containing AF and subsequent excretion via the foetal kidneys.
CONCLUSIONS: The study shows evidence, for the first time, of the foetal exposure to gluten immunogenic peptides and establishes a positive correlation with maternal gluten intake. The results obtained point to a novel physiological concept as they describe a plausible closed-loop circuit entailing foetal swallowing of GIP contained in AF and its subsequent excretion through the foetal kidneys. The study adds important new information to understanding the coeliac exposome.
摘要:
背景:乳糜泻发病率的增加导致人们对积极寻找相关因素的兴趣与日俱增,甚至子宫内和早期生活。最近强调了从概念开始的疾病暴露方法涵盖了生命过程的观点。子宫内早期接触谷蛋白免疫原性肽(GIP)的知识可能会挑战早期产前耐受或炎症的时间顺序,而不是婴儿出生后的固体饮食。
方法:我们开发了一种准确而特异的免疫测定方法来检测羊水(AF)中的GIP,并研究了它们的积累,吞咽房颤导致的排泄动力学和胎儿暴露。招募了125名具有不同麸质饮食和胎龄的孕妇。
结果:在至少第16孕周开始的富含麸质的妇女中,在房颤中可以检测到GIP。虽然在妊娠期间没有观察到GIP水平的显著差异,羊水GIP妊娠晚期未因孕妇禁食而改变,提示闭环需要胎儿吞咽含GIP的AF,随后通过胎儿肾脏排泄。
结论:研究显示,第一次,胎儿暴露于谷蛋白免疫原性肽,并与母体谷蛋白摄入量呈正相关。获得的结果指向一个新的生理概念,因为它们描述了一个合理的闭环回路,需要胎儿吞下AF中所含的GIP并随后通过胎儿肾脏排泄。这项研究为理解腹腔暴露增加了重要的新信息。
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