Commensal Skin Microbiota Modulate Responses to Ultraviolet Radiation in Humans.

Abstract

The skin and its commensal microbiota are regularly exposed to ultraviolet radiation (UVR) in sunlight. While UVR is a major environmental factor affecting human skin, the influence of skin microbiota on skin's UVR response remains underexplored. We have investigated the impact of the skin microbiota on UVR-induced inflammation (sunburn response) in healthy humans (Fitzpatrick skin type I-III, n = 10). Ethanol-disinfected and non-disinfected upper back skin of 10 healthy volunteers were exposed to a geometric series of solar-simulated UVR (SSR, erythemally-weighted, 7-80mJ/cm2). Erythema was assessed 24 h post-exposure visually and using reflectance spectroscopy. Skin biopsies were collected 0.5 h and 24 h after exposure to 80 mJ/cm2 SSR and from unexposed skin. Keratinocyte apoptosis (TUNEL, cleaved caspase-3), proliferation (Ki67), and dermal inflammatory infiltrate (CD68, neutrophil elastase, CD4) were assessed by immunostaining. Gene expression and pathway enrichment were analysed using Xenium spatial transcriptomics. Disinfected and non-disinfected skin exhibited similar minimal erythema doses, with no significant difference in the UVR-erythema dose-response. Disinfection had no detectable effect on the measured outcomes in unexposed skin. At 0.5 h post-exposure, disinfected skin responded similarly to non-disinfected skin across all measured parameters. However, at 24 h post-exposure, disinfected skin showed significantly fewer TUNEL+ keratinocytes (P = 0.0005), CD68+ macrophages (P = 0.012), and neutrophil elastase+ neutrophils (P = 0.012), together with increased Ki67+ keratinocyte proliferation (P = 0.020) compared with non-disinfected skin. Spatial transcriptomic analysis supported these findings, showing upregulation of proliferation-associated genes and pathways in disinfected skin, whereas apoptosis- and inflammation-associated pathways were enriched in non-disinfected skin. These findings suggest that the healthy skin microbiota modulates human skin's response to UVR, promoting keratinocyte apoptosis and dermal infiltration of neutrophils and macrophages while reducing keratinocyte proliferation.