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

Abstract

Atopic dermatitis (AD) is a highly prevalent inflammatory skin disease in which cutaneous microbial dysbiosis is related to disease pathophysiology. AD skin is often infected by Staphylococcus aureus and its abundance is associated with disease severity and response to treatment, possibly due to the reported low levels of antimicrobial peptides (AMPs) in AD lesional skin. Therapeutic targeting of the skin microbiome and AMP levels in AD skin is therefore important to restore skin homeostasis and combat AD. We analyzed the skin microbiome composition in 7 AD patients and 10 healthy volunteers upon topical coal tar (CT) or vehicle treatment. We implemented and validated a novel Staphylococcus specific single-locus sequence typing (SLST) 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. Using SLST, we found that Staphylococcus aureus-like and Staphylococcus capitis-like taxa decreased during treatment. We identified a hitherto unknown therapeutic mode of action of CT, namely the induction of AMPs in keratinocytes via activation of the aryl hydrocarbon receptor (AHR). Additional to the previously reported induction of filaggrin and other skin barrier-related proteins by CT, 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 work underscores the importance of CT in the therapeutic AD armamentarium and highlights the AHR as a target for drug development.