Skin commensal Cutibacterium acnes alleviates UVB-induced solar dermatitis via ceramide-mediated TLR4-MyD88-NF-κB

The high-altitude environment is characterized by hypobaric hypoxia and intense ultraviolet B (UVB) radiation, contributing to increased incidence of UVB-induced skin injuries, including plateau solar dermatitis (PSD). The role of commensal skin microbiota in mediating photoprotection under such extreme conditions remains poorly understood. This study aimed to identify UVB-protective skin microbiota in high-altitude populations and to elucidate their potential mechanisms in mitigating UVB-induced skin damage.

Skin microbiota profiles were analyzed by 16S rRNA gene sequencing in healthy plateau residents and PSD patients. Protective effects were evaluated using a murine model of UVB-induced skin injury and an in vitro UVB-exposed HaCaT keratinocyte model. Integrated transcriptomic, proteomic, and metabolomic analyses were performed to identify candidate bioactive microbial metabolites, followed by functional validation.

Cutibacterium acnes (C. acnes) was significantly enriched in healthy plateau residents compared with PSD patients. Topical application of C. acnes alleviated UVB-induced skin inflammation, collagen degradation, and DNA damage in mice. Multi-omics analyses revealed dysregulation of sphingolipid metabolism following UVB exposure and highlighted bacterial-derived ceramides as candidate protective metabolites. Two representative ceramides, CER2 and CER14, significantly reduced UVB-induced apoptosis, oxidative stress, and DNA damage in keratinocytes. These effects were associated with suppression of TLR4-MyD88-NF-κB signaling activity.

This study identifies C. acnes as a commensal bacterium with photoprotective potential against UVB-induced skin damage in high-altitude environments. Ceramide-related lipid metabolites derived from C. acnes contribute to attenuation of UVB-triggered inflammatory signaling and cellular injury, providing new insights into microbiome-based strategies for photoprotection.