Commensal Skin Microbiota Modulate Responses to Ultraviolet Radiation in Humans
Wen Duan, Mark D Farrar, Anne N Chandidzura, Michael Peake, Bezaleel Mambwe, Abigail K Langton, Andrew J McBain, Lesley E Rhodes, Catherine A O’NeillAbstract
Background
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.
Objectives
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).
Methods
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.
Results
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.
Conclusions
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.