Ultraviolet Radiation Reshapes the Metabolome of Skin Commensal Bacteria, Influencing AhR Signalling and Barrier Function

Le résumé fourni par la source

Ultraviolet radiation (UVR) is an environmental stressor to the skin and its associated microbiota. Many commensal bacteria produce tryptophan-derived metabolites that modulate epidermal barrier function through aryl hydrocarbon receptor (AhR) signalling. However, the effects of UVR on these metabolic outputs and the subsequent effects on skin barrier function remains unclear. This study examined these interactions. Individual skin commensal bacteria were irradiated with 37.5mJ/cm² or 150mJ/cm² of solar-simulated radiation (SSR). Cell-free supernatants (CFSNs) were collected and analysed for tryptophan metabolites (using LC-MS), untargeted metabolites (using GC-MS), and AhR agonist activity (via a reporter assay). The effects on barrier function were assessed by measuring transepithelial electrical resistance (TEER) of CFSN-treated keratinocyte cultures. Time-course expression of tryptophan-related genes after irradiation was measured by qPCR. Unirradiated bacterial metabolomes were species-specific. Following irradiation, the abundance of metabolites generated by the indole-pathway generally increased after 37.5mJ but decreased following 150mJ. Untargeted analyses revealed several decreases in amino and organic acid production after high-dose SSR, while 37.5mJ resulted in fewer changes. Low-dose SSR upregulated genes involved in tryptophan metabolism (ipdC, ALDH) and synthesis (trpE). AhR agonism increased in 10/12 organisms following irradiation, statistically correlating with increased levels of indole-pathway metabolites (indole-3-acetamide, tryptophol, indole-3-carboxaldehyde, and tryptamine). Keratinocytes treated with irradiated S. hominis, M. luteus, and S. capitis CFSNs showed enhanced TEER, concurrent with increased AhR activation; inhibiting the AhR removed this effect. UVR significantly alters the metabolomes of skin commensal bacteria, with knock on effects for AhR signalling and barrier integrity, potentially influencing the skin’s response to UVR.

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