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 lifecourse 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. 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. 119 pregnant women with different gluten diets and gestational ages were recruited. 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. The study shows evidence, for the first time, of the fetal exposure to gluten immunogenic peptides, and establish a positive correlation with maternal gluten intake. The results obtained point to a novel physiological concept as they describe a closed-loop circuit entailing fetal swallowing of GIP contained in AF, and its subsequent excretion through the fetal kidneys. The study adds important new information to understanding the coeliac exposome.

The authors have declared no competing interest.

This study was funded by grant from I+D+I FEDER Andalucia 2014-2020 (US-15332), and Federacion de Asociaciones de Celiacos de Espana (FACE) (SUBN/2019/005). Maria Gonzalez-Rovira received a fellowship from the University of Seville, Spain (PIF del VI Plan Propio de Investigacion y Transferencia II.2A).

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This study was conducted in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the Sevilla Sur Provincial Research Ethics Committee (CEI Sevilla-Celifluid, Sevilla, Spain) for samples from Virgen de Valme University Hospital and Quironsalud Sagrado Corazon Hospital (Seville, Spain) and by the Regional Hospital La Paz Research Ethics Committee (CEI-HULP-PI-2611, Madrid, Spain) for samples from La Paz University Hospital (Madrid, Spain). Written informed consent was obtained from all the participants. The participants consented to IdiPaz for the use of their data and/or samples for health-related research purposes.

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