Intestinal defensin secretion in infancy is associated with the emergence of sensitization and atopic dermatitis.

ABSTRACT

BACKGROUND: Intestinal flora and innate immunity, and their interactions impact adaptive immunity. OBJECTIVE: To study the association of fecal defensin levels in infancy with synbiotic treatment and with the emergence of atopy. METHODS: The randomly selected group of 102 infants belonged to a randomized, double-blind placebo-controlled trial where 1223 infants in high risk for allergy received, from birth to 6 months, a mixture of synbiotics, or placebo. Clinical trials registration number for the clinical trial is NCT00298337. In the subgroup, 45 received active treatment and 56 received placebo treatment. Follow-up for the emergence of sensitization and allergic diseases lasted 5 years. At the age of 3 (n = 96) and 6 (n = 87) months, we measured fecal levels of human neutrophil peptide (HNP) 1-3 and of ß-defensin 2 (HBD2) using enzyme linked immunosorbent assays and concentrations of lactic acid bacteria on MRS agar. We used multifactorial regression in data analysis. RESULTS: Fecal levels of HNP1-3 and HBD2 decreased from the age of 3-6 months (P < 0.0001). HBD2 levels decreased less in the synbiotics group compared with placebo (P < 0.02). High fecal HBD2 levels at 6 months were associated with an increased risk for sensitization by the age of 5 years (OR 2.5, 95% confidence interval 1.1-5.8, P < 0.03). High fecal HNP1-3 levels at 6 months were associated with a decreased risk for atopic dermatitis (OR 0.4, 95% CI 0.1-1.0, P < 0.05). Samples with very low or high HBD2 levels at 6 months had low concentrations of lactic acid bacteria (P < 0.02). CONCLUSIONS AND CLINICAL RELEVANCE Early innate immunity responses in the gut are associated with the emergence of sensitization and atopic dermatitis later in childhood.