Fetal-maternal interactions with gluten immunogenic peptides during pregnancy: a new determinant on the coeliac exposome

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.