BACKGROUND: Polymorphic light eruption (PLE) is the most frequent photodermatosis in Europe with an estimated prevalence of 10 to 20%, particularly in temperate climates. Itching or burning lesions appear only in sun-exposed areas, predominantly on the chest, the arms and forearms within a few hours following exposure. The disease's cause is still unknown, yet studies have suggested that skin microbial elements may play a role in its pathogenesis. OBJECTIVES: We investigated in this cohort the skin microbiome of PLE patients upon exposure to ultraviolet radiation (UVR), to assess its role in the onset of PLE lesions. METHODS: Forty-one skin swabs have been collected from eleven PLE patients at baseline and following a three-day exposure to UVR and from healthy controls. The collected swabs were analyzed for their microbial composition using a 16S amplicon sequencing approach. RESULTS: The PLE skin showed a dysbalanced microbiome, already at baseline, with significantly reduced microbial diversity and noticeable colonization by bacterial pathogens as Staphylococcus aureus. Upon UVR exposure, the PLE microbiome exhibited a further loss of diversity and decline of beneficial skin commensals. In line with this, we observed that UVR exerted strong antimicrobial effects in vitro against representative skin residents. CONCLUSIONS: Taken together, UVR can lead to profound skin microbiome changes, allowing the proliferation of dysbiotic members that can release a variety of elements able to trigger PLE lesions. This is the first study investigating the cutaneous microbiome changes in PLE patients upon UVR, offering new insights into disease pathogenesis, so far unexplored.