Influence of early environmental factors on lymphocyte subsets and gut microbiota in infants at risk of celiac disease; the PROFICEL study / Influencia de factores ambientales tempranos sobre las subpoblaciones de linfocitos y la microbiota intestinal de niños con riesgo de desarrollar enfermedad celíaca; el Estudio PROFICEL

Introduction: 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. Aim: To assess the associations between early environmental factors (EEF), lymphocyte subsets, and intestinal microbiota composition in infants at familial risk for CD. Study design: Prospective observational study. Subjects: 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. Methods: Lymphocyte subsets and gut microbiota composition were studied at the age of 4 months. Results: 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. Conclusions: 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 (AU)

Introducción: Es bien sabido que el genotipo HLA puede explicar un 40% del riesgo genético de enfermedad celíaca, por lo que otros factores de predisposición genéticos así como factores que sutilmente modulen la activación y diferenciación de células T necesitan ser estudiados. Esto incluye factores ambientales, de los que se cree actualmente que ejercen un efecto sobre el desarrollo del sistema inmune y la microbiota intestinal. Objetivo: Evaluar las asociaciones entre factores ambientales tempranos, las subpoblaciones de linfocitos y la composición de la microbiota intestinal en niños con riesgo familiar de enfermedad celíaca. Diseño del estudio: Estudio prospectivo observacional Sujetos: 55 niños de 4 meses de edad con al menos un familiar celíaco de primer grado. Los niños fueron clasificados de acuerdo al tipo de parto, ingesta materna de antibióticos durante el embarazo y durante el parto, tipo de lactancia, infecciones tempranas y toma de antibióticos, administración de la vacuna de rotavirus, y incidencia de alergias dentro de los 18 primeros meses de vida. Métodos: Las subpoblaciones de linfocitos y la composición de la microbiota intestinal fueron estudiadas a la edad de 4 meses. Resultados: La lactancia de fórmula y las infecciones tempranas se asociaron con un mayor número absoluto de células CD3+, CD4+, CD4+CD38+, CD4+CD28+ y CD3+CD4+ CD45RO+ (P0.01). El parto por cesárea y la administración de la vacuna de rotavirus se asociaron a un menor porcentaje de células CD4+CD25+. La toma temprana de antibióticos se asoció y correlacionó con menor número de Bifidobacterium longum y mayor número de Bacteroides fragilis. Conclusiones: Las infecciones y la toma de antibióticos en los primeros 4 meses de edad son los factores ambientales tempranos más fuertemente y/o frecuentemente asociados a las subpoblaciones de linfocitos y la composición de la microbiota, respectivamente, en niños con riesgo de enfermedad celíaca (AU)

Influence of milk-feeding type and genetic risk of developing coeliac disease on intestinal microbiota of infants: the PROFICEL study.

Interactions between environmental factors and predisposing genes could be involved in the development of coeliac disease (CD). This study has assessed whether milk-feeding type and HLA-genotype influence the intestinal microbiota composition of infants with a family history of CD. The study included 164 healthy newborns, with at least one first-degree relative with CD, classified according to their HLA-DQ genotype by PCR-SSP DQB1 and DQA1 typing. Faecal microbiota was analysed by quantitative PCR at 7 days, and at 1 and 4 months of age. Significant interactions between milk-feeding type and HLA-DQ genotype on bacterial numbers were not detected by applying a linear mixed-model analysis for repeated measures. In the whole population, breast-feeding promoted colonization of C. leptum group, B. longum and B. breve, while formula-feeding promoted that of Bacteroides fragilis group, C. coccoides-E. rectale group, E. coli and B. lactis. Moreover, increased numbers of B. fragilis group and Staphylococcus spp., and reduced numbers of Bifidobacterium spp. and B. longum were detected in infants with increased genetic risk of developing CD. Analyses within subgroups of either breast-fed or formula-fed infants indicated that in both cases increased risk of CD was associated with lower numbers of B. longum and/or Bifidobacterium spp. In addition, in breast-fed infants the increased genetic risk of developing CD was associated with increased C. leptum group numbers, while in formula-fed infants it was associated with increased Staphylococcus and B. fragilis group numbers. Overall, milk-feeding type in conjunction with HLA-DQ genotype play a role in establishing infants' gut microbiota; moreover, breast-feeding reduced the genotype-related differences in microbiota composition, which could partly explain the protective role attributed to breast milk in this disorder.