Abstract
Gaining a deeper understanding of the variation in skin microbiota across habitats and layers provides critical insights into the complex host-microbial interactions that drive inflammatory skin diseases. Our study investigated dermal versus epidermal microbiota in lesional and non-lesional skin of 37 adult atopic dermatitis (AD) patients and 37 healthy controls. Skin biopsies were partitioned into epidermal and dermal compartments, while serial tape strips collected the superficial epidermis. Bacterial communities were analyzed by cultivation, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, confocal laser scanning microscopy, and metagenomic sequencing. We found that the effects of AD were evident across skin layers. The natural variation between skin layers and habitats diminishes in AD-affected skin, intensifying the impact of the microenvironment and host factors. A remarkably distinct dermal bacterial community was discovered among AD patients, being more conserved and providing a clearer difference between skin habitats, while the epidermis varied substantially. Importantly, comparisons between AD patients and controls revealed more genera differed when studying the dermal samples than the epidermal ones. Staphylococcus, Corynebacterium, and Cutibacterium genera differed with AD status across all samples, but Prevotella and Mitsuokella only differed in the dermis. In the dry and moist dermis, this translated into 14 and 61 gene pathways significantly varying with AD status, including many related to the biosynthesis of menaquinones (vitamin K2). These results suggest dermal sampling would allow for the role of the skin microbiome within AD pathogenesis to be better resolved since these communities are simpler and less prone to environmental contamination. IMPORTANCE: This study sheds light on the profound impact of skin microbiota's complex composition and distribution in atopic dermatitis (AD). The distinctive bacterial profile and activity, especially within the dermal skin compartment, vividly mirrored the cutaneous conditions in this inflamed microenvironment. The striking similarity in bacterial communities across different skin habitats in atopic skin underscores the high influence of atopic dermatitis-the genetic predisposition to an amplified immune response. This finding suggests that the dermal bacterial profile could be a valuable tool for longitudinally monitoring changes during the disease's relapsing phases, allowing for a precise categorization of patients into specific AD endotypes. Broadening the focus throughout the entire eczema-affected skin paves the way for treatments capable of modulating dermal biological factors, offering more effective management of AD. By further centering the interest in host-microbial interactions, we can refine personalized treatments, ultimately improving the lives of millions suffering from atopic dermatitis.