Impact of polycyclic aromatic hydrocarbons on the skin microbiome and epidermal barrier function

Summary: Abstract Body: Polycyclic aromatic hydrocarbons (PAH) are environmental pollutants present in airborne particulate matter, cigarette smoke, and fire smoke. PAHs are known to activate AhR, resulting in ROS production, inflammation and DNA damage after inhalation and ingestion. Research on dermal exposure, particularly the skin microbiome, remains nascent. This study aims to investigate the effects of PAHs on the skin microbiome and to evaluate whether commensals can support epidermal barrier integrity. Human epidermal equivalents (HEEs) were colonized with individual species (S. epidermidis, S. warneri, S .haemolyticus, M. luteus, C. aurimucosum) or with a microbiota consortium of skin bacterial isolates (Flowers Flora 5), simulating a representative model of skin microbiota diversity and function. Bacterial colonization was maintained for 72h, monitored by CFU counting and Gram staining. Colonized and uncolonized HEEs were exposed topically to a multi-component PAH solution. PAH exposure did not affect bacterial growth, as CFU counts remained stable over 72 hours. In contrast, growth assays in TSB revealed a dose-dependent inhibitory effect of PAH on S. epidermidis and S. warneri, highlighting differential bacterial responses in the presence and absence of the host. PAH exposure significantly upregulated CYP1A1 and CYP1B1, indicating AhR activation, while altering key epidermal differentiation markers (KRT10, DSC1, HRNR and IVL), suggesting impaired barrier homeostasis. Notably, bacterial colonization mitigated PAH-induced barrier dysfunction, as evidenced by the restoration of KRT10 and DSC1 in colonized HEEs. Additionally, PAH exposure markedly increased IL1A and IL1B expression. However, colonization with M. luteus significantly suppressed IL-1β release, highlighting an anti-inflammatory effect of commensal bacteria. Overall, our results highlight the potential of leveraging the skin microbiome as a therapeutic target to protect the epidermal barrier from environmental pollutants such as PAH. Deborah C. Minzaghi¹, Stephen Prouty¹, Simon Knight¹, Thomas Sutter², Elizabeth Grice¹ 1. Dermatology, University of Pennsylvania, Philadelphia, PA, United States. 2. Biological Sciences, The University of Memphis, Memphis, TN, United States. Innate Immunity, Microbiology, and Microbiome