Assessment of microbiome-UV interactions in a physiological ex vivo human skin model

Introduction The cutaneous microbiome is increasingly recognized as a modulator of skin physiology and UV responses, yet mechanistic studies in human models remain limited by the lack of model systems that preserve physiologically relevant skin architecture and microbial communities. Methods We used the physiological Perfex ex vivo human skin explant system to assess microbiome-UV interactions. Abdominal skin explants from three donors were inoculated with donor-specific cheek microbiomes or vehicle, and, after 24 h, exposed or not to a single UV irradiation. Assessments were performed 48 h after inoculation. Bacterial survival and transfer were evaluated by culture-based CFU enumeration and 16S rRNA gene sequencing. Cutaneous responses were assessed by RT-qPCR for 29 genes involved in oxidative stress, inflammation, skin hydration, barrier function, and epidermal differentiation. Cyclobutane pyrimidine dimers (CPDs), 8-hydroxy-2′-deoxyguanosine (8-OHdG), oxidized proteins, and NRF2 were quantified by immunohistochemistry. Results Perfex explants supported short-term persistence of donor-derived skin microbiota for up to 48 h, although cultivable bacteria decreased by approximately 90% over this period, including upon UV irradiation. 16S profiles confirmed donor-specific microbiome transfer but also revealed residual bacterial DNA in uninoculated controls, limiting interpretation of UV effects on microbial composition. Assessing expression changes in 29 epidermal genes examined, four—GPX1, IVL, LOR, and KRT1—exhibited UV-induced expression patterns that differed according to the presence or absence of the microbiome. By contrast, microbiome inoculation markedly attenuated UV-induced CPDs, 8-OHdG, protein oxidation, and NRF2 induction. Discussion Despite substantial limitations in microbial engraftment, viability, and temporal resolution, the Perfex system provides a physiologically relevant ex vivo platform in which a transplanted human skin microbiome could modulate UV-induced oxidative and genotoxic damage. These proof-of-concept data support further refinement of this model for mechanistic microbiome-UV studies.