The glycerol fermentation of probiotic Staphylococcus epidermidis (S. epidermidis) in the skin microbiome produced butyric acid in vitro at concentrations in the millimolar range. The exposure of dorsal skin of mice to ultraviolet B (UVB) light provoked a significant increased production of pro-inflammatory interleukin (IL)-6 cytokine. Topical application of butyric acid alone or S. epidermidis with glycerol remarkably ameliorated the UVB-induced IL-6 production. In vivo knockdown of short-chain fatty acid receptor 2 (FFAR2) in mouse skin considerably blocked the probiotic effect of S. epidermidis on suppression of UVB-induced IL-6 production. These results demonstrate that butyric acid in the metabolites of fermenting skin probiotic bacteria mediates FFAR2 to modulate the production of pro-inflammatory cytokines induced by UVB.

Introduction: Acne vulgaris afflicts many people, and despite the multitude of the anti-acne products on the market, there is still no effective treatment that can prevent and cure this disease. The severity of acne vulgaris is highly associated with the inflammatory response to Propionibacterium acnes (P. acnes) now referred to as Cutibacterium acnes (C. acnes), an opportunistic skin bacterium in the human skin microbiome. Areas covered: We here provide the prospects of creating acne vaccines targeting secreted virulence factors of C. acnes including secretory Christie-Atkins-Munch-Peterson (CAMP) factor. Neutralization of secreted virulence factors by either active or passive vaccination may have a lower risk of disturbing the microbial ecosystem in the human skin microbiome. Expert opinion: Major steps could be taken to start a public vaccination program at an early age to prevent the future occurrence of acne vulgaris. Future therapeutic monoclonal antibodies can be designed to specifically neutralize virulence factors of C. acnes including CAMP factors without disrupting the optimal balance of C. acnes in the human skin microbiome and lowering the risk of creating drug-resistant C. acnes. Targeting secreted virulence factors without disturbing the commensal relationship of host can be a novel gateway towards the therapeutic treatment of acne vulgaris.

Bacteria that use electron transport proteins in the membrane to produce electricity in the gut microbiome have been identified recently. However, the identification of electrogenic bacteria in the skin microbiome is almost completely unexplored. Using a ferric iron-based ferrozine assay, we have identified the skin Staphylococcus epidermidis (S. epidermidis) as an electrogenic bacterial strain. Glycerol fermentation was essential for the electricity production of S. epidermidis since the inhibition of fermentation by 5-methyl furfural (5-MF) significantly diminished the bacterial electricity measured by voltage changes in a microbial fuel cell (MFC). A small-scale chamber with both anode and cathode was fabricated in order to study the effect of ultraviolet-B (UV-B) on electricity production and bacterial resistance to UV-B. Although UV-B lowered bacterial electricity, a prolonged incubation of S. epidermidis in the presence of glycerol promoted fermentation and elicited higher electricity to suppress the effect of UV-B. Furthermore, the addition of glycerol into S. epidermidis enhanced bacterial resistance to UV-B. Electricity produced by human skin commensal bacteria may be used as a dynamic biomarker to reflect the UV radiation in real-time.

UVB-induced skin damage results in various inflammatory disorders through the induced generation of reactive oxygen species (ROS) that quickly inundate tissue antioxidants and chronic disorders; in severe cases it can lead to skin cancer. We investigated efficacies of human skin commensal bacteria S. epidermidis (ATCC12228) with glycerol, which on fermentation produces electrons. In vivo affirmation on ICR mice has confirmed the antioxidative role of topically applied S. epidermidis with glycerol against UVB irradiation and maintained sufficient expression of 4-hydroxynonenal (4-HNE) and cyclobutane pyrimidine dimer (CPD), a major biomarker for lipid peroxidation and DNA damage. Upon UVB irradiation in keratinocyte cell lines treated with glycerol mediated S. epidermidis fermentation product show the reduced intracellular oxidative stress. S. epidermidis or glycerol alone in In vivo topical application in mice skin and in vitro fermentation product treatment in keratinocytes does not influence the level of oxidative stress. Further electrochemical behavior of glycerol mediated S. epidermidis fermented medium found to produce electron transfer; this result suggests the electrogenic and antioxidant property of S. epidermidis. The electrons produced by S. epidermidis fermentation product initiate reduction of free radicals by converting toxic Fe3+ (ferric ion) back to nontoxic Fe2+ (ferrous ion); thereby it terminates Fenton’s reaction and maintains iron hemostasis. The novel pathway linking electrons produced by probiotic skin bacteria and iron metabolism has been further analyzed. Note: This abstract was not presented at the conference. Citation Format: Arun Balasubramaniam, Sunita Keshari, Prakaso Adi, Chun-Ming Huang. The human skin bacteria Staphylococcus epidermidis ameliorates UVB-induced free radicals through reduction of labile iron [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B22.