Potential therapeutic application of skin microbiomes in the treatment of various skin disease

Abstract

A diverse microbiome exists within the skin, and its imbalance is related to skin inflammation and disease. In addition, disruption of the skin's microbiota can have a negative impact on the prognosis and treatment of certain diseases of the skin. In this study, we investigated the effects and mechanisms of external irritants such as PM2.5 and Staphylococcus aureus (SA) exposure in HaCaT keratinocytes. When PM2.5 is present in HaCaT cells, it stimulates the production of reactive oxygen species (ROS), causing mitochondrial dysfunction and intrinsic mitochondrial apoptosis. Furthermore, SA, for example, can change the distribution or prevalence of certain microbial species on the skin, which may impact the development of severe atopic dermatitis (AD) or psoriasis (Pso). It has been shown that external stimulants, such as PM2.5 and SA, alter the AhR signaling pathway, causing abnormal increase in cellular oxidative stress, modulating immune cell imbalance, and failing to restore gene expression involved in skin barrier formation. In the case of a disruption of the skin barrier in response to PM2.5 accumulation or SA colonization, high levels of T helper 2 (Th2)-derived cytokines may be produced, resulting in an imbalance between T helper 1, T helper 2, and T helper 17 cells. Therefore, potential therapeutic skin microbiomes were investigated in this study, including Staphylococcus epidermidis WF2R11, Cutibacterium avidum R-CH3 and Staphylococcus hominis R9, which reduced inflammatory cytokines and restored skin barrier function genes by activating the aryl hydrocarbon receptor (AhR) and nuclear factor erythroid-2-related factor 2 (Nrf2). Using a culture medium derived from a particular functional skin microbe, we observed that PM2.5 or SA-mediated activation of the AhR pathway significantly reduced oxidative stress in HaCaT cells. Moreover, our results suggest that our potentially therapeutic skin microbiomes can prevent Th2-biased skin barrier disruption through IL-13 and IL-4-dependent FLG deregulation, STAT3 activation, and AhR-mediated STAT6 expression. The significance of applying skin microbiome interventions in the treatment of inflammatory skin diseases is thus highlighted by our findings.