Interactions Between IL-17 Variants and Streptococcus 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 IL-17 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 Streptococcus were analyzed. IL-6 and IL-8 in the human intestinal epithelial cell line (HIEC-6) were measured after stimulation of IL-17 and Streptococcus mitis. RESULTS: In this study, Streptococcus was enriched in infants with AD and was higher in those with the GA + AA of IL-17 (rs2275913) variant. Streptococcus was positively correlated with IgE and SCORAD in infants with AD and GA + AA of IL-17. Butyrate and valerate were negatively correlated with Streptococcus and were decreased in infants with AD and GA + AA. Bacterial genes for oxidative phosphorylation induced by reduced colonization of Clostridium 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 S. mitis-stimulated HIEC-6 cells. CONCLUSIONS: These findings suggest that increased Streptococcus and A allele of IL-17 (rs2275913) may contribute to the pathogenesis of AD via modulation of the immune system in infancy.