Potential Therapeutic Skin Microbiomes Suppressing Staphylococcus aureus-Derived Immune Responses and Upregulating Skin Barrier Function-Related Genes via the AhR Signaling Pathway
Eulgi Lee; Kyungchan Min; Hyeok Ahn; Bu-nam Jeon; Shinyoung Park; Changhee Yun; Hyehee Jeon; Jae-sung Yeon; Hyun Kim; Hansoo Park
Disruption of the skin microbial balance can exacerbate certain skin diseases and affect prognosis and treatment. Changes in the distribution and prevalence of certain microbial species on the skin, such as Staphylococcus aureus (SA), can impact the development of severe atopic dermatitis (AD) or psoriasis (Pso). A dysfunctional skin barrier develops in AD and Pso due to SA colonization, resulting in keratinization and chronic or progressive chronic inflammation. Disruption of the skin barrier following SA colonization can elevate the production of T helper 2 (Th2)-derived cytokines, which can cause an imbalance in Th1, Th2, and Th17 cells. This study examined the ability of potential therapeutic skin microbiomes, such as Cutibacterium avidum R-CH3 and Staphylococcus hominis R9, to inhibit SA biofilm formation and restore skin barrier function-related genes through the activation of the aryl hydrocarbon receptor (AhR) and the nuclear factor erythroid-2-related factor 2 (Nrf2) downstream target. We observed that IL-4/IL-13-induced downregulation of FLG, LOR, and IVL induced by SA colonization could be reversed by dual AhR/Nrf2 activation. Further, OVOL1 expression may be modulated by functional microbiomes via dual AhR/Nrf2 activation. Our results suggest that our potential therapeutic skin microbiomes can prevent SA-derived Th2-biased skin barrier disruption via IL-13 and IL-4-dependent FLG deregulation, STAT3 activation, and AhR-mediated STAT6 expression.
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