Interactions Between Variants and in the Gut Contribute to the Development of Atopic Dermatitis in Infancy.

Purpose: Interleukin (IL)-17 variants and perturbations in the gut microbiota may influence the development of atopic dermatitis (AD). However, unifying principles for variants of host and microbe interaction remains unclear. We sought to investigate whether variants and gut microbiota affect the development of AD in infancy.

Methods: Composition of the gut microbiota was analyzed in fecal samples from 99 normal healthy and 61 AD infants at 6 months of age. The associations between total immunoglobulin E (IgE), the scoring atopic dermatitis (SCORAD), short-chain fatty acids, transcriptome and functional profile of the gut measured in these subjects and were analyzed. IL-6 and IL-8 in the human intestinal epithelial cell line (HIEC-6) were measured after stimulation of IL-17 and .

Results: In this study, was enriched in infants with AD and was higher in those with the GA + AA of (rs2275913) variant. was positively correlated with IgE and SCORAD in infants with AD and GA + AA of . Butyrate and valerate were negatively correlated with and were decreased in infants with AD and GA + AA. Bacterial genes for oxidative phosphorylation induced by reduced colonization of were decreased compared with normal and GG. In transcriptome analysis, lactate dehydrogenase A-like 6B was higher in infants with AD compared with healthy infants. IL-6 and IL-8 were increased in IL-17 and/or -stimulated HIEC-6 cells.

Conclusions: These findings suggest that increased and A allele of (rs2275913) may contribute to the pathogenesis of AD via modulation of the immune system in infancy.