TARgeting the cutaneous microbiota in atopic dermatitis by coal tar via AHR-dependent induction of antimicrobial peptides.

Abstract Skin colonization by Staphylococcus aureus and its relative abundance is associated with atopic dermatitis (AD) disease severity and treatment response. Low levels of antimicrobial peptides (AMPs) in AD skin may be related to the microbial dysbiosis. Therapeutic targeting of the skin microbiome and AMP expression can therefore restore skin homeostasis and combat AD. In this study, we analyzed the cutaneous microbiome composition in 7 AD patients and 10 healthy volunteers upon topical coal tar (CT) or vehicle treatment. We implemented and validated a Staphylococcus specific single-locus sequence typing approach combined with classic 16S rRNA marker gene sequencing to study the bacterial composition. During CT treatment, Staphylococcus abundance decreased and Propionibacterium abundance increased, suggesting a shift of the microbiota composition towards that of healthy controls. We furthermore identified a hitherto unknown therapeutic mode of action of CT, namely the induction of keratinocyte-derived AMPs via activation of the aryl hydrocarbon receptor (AHR). Restoring AMP levels in AD skin via AHR-dependent transcription regulation can be beneficial by creating an (anti-)microbial milieu that is less prone to infection and inflammation. This underscores the importance of CT in the therapeutic AD armamentarium and highlights the AHR as a target for drug development.