Influence of early environmental factors on lymphocyte subsets and gut microbiota in infants at risk of celiac disease; the PROFICEL study.

Abstract

It is known that the HLA genotype can explain about a 40% of the genetic risk of celiac disease (CD), thus, other genetic predisposing factors as well as factors that subtly modulate T cell activation and differentiation need to be studied. This includes environmental factors that are currently believed to impact on the immune system and gut microbiota development. To assess the associations between early environmental factors (EEF), lymphocyte subsets, and intestinal microbiota composition in infants at familial risk for CD. Prospective observational study. Fifty-five 4 month-old infants with at least a first-degree relative suffering CD. Infants were classified according to type of delivery, mother's antibiotic intake during pregnancy and during labor, milk-feeding practices, early infections and antibiotic intake, rotavirus vaccine administration, and allergy incidence within the first 18 months of life. Lymphocyte subsets and gut microbiota composition were studied at the age of 4 months. Formula feeding and infant's infections were associated with higher CD3+, CD4+, CD4+CD38+, CD4+CD28+ and CD3+CD4+CD45RO+ counts (P0.01). Infant s infections were also associated with higher CD4+CD25+, CD4+HLA-DR+ and NK cell counts (P0.01). Cesarean delivery and rotavirus vaccine administration were associated with lower percentage of CD4+CD25+ cells. Infant's antibiotic intake was associated and correlated with lower counts of Bifidobacterium longum and higher counts of Bacteroides fragilis group. Infant s infections and antibiotic intake in the first 4 months of life are the EEF more strongly and/or frequently associated to lymphocyte subpopulations and microbiota composition, respectively, in infants at risk of CD.