痤瘡桿菌 (P. acnes) 在人類微生物相的過度生長可視為微生物失衡在青春痘的現象。我們以前發表的文章已證實皮膚葡萄球菌 (S. epidermidis) 在青春痘內是一種會發酵的益生菌。此菌可利用發酵產生短鏈脂肪酸 (SCFAs) 以降低P. acnes 的過度生長。 然而，因為每個人青春痘內的 S. epidermidis 數量皆不同，因此很難知道要用多少益生菌或益生元 (Prebiotic) 來治療青春痘。為了克服此困難，本計劃將發展青春痘發酵益生菌貼膠。S. epidermidis 在貼膠內發酵後，便立刻被殺死，此發酵益生菌貼膠便產生均勻量的 SCFAs 以克制 P. acnes 的生長。我們將用老鼠耳朵發炎及3D培養人類皮脂腺細胞模式來驗證發酵益生菌貼膠的功效，並調查其抗菌及降低發炎生物因子 (IL-6, MIP-2(IL-8), IL-1 beta)的能力。 我們假設發酵益生菌貼膠能產生相同量的 SCFAs 給予每個青春痘傷口治療。三個目標證實我們的假說。目標一，當 S. epidermidis 在貼膠內發酵後，我們將殺死 S. epidermidis，並將貼膠內的 SCFAs 有效導入 P. acnes 所引起的青春痘傷口內。目標二，我們將檢查是否貼膠可殺死各種型態的 P. acnes 並明顯降低 P. acnes 所引起的發炎反應。目標三，我們將比較貼膠與單獨 SCFA 的功效並檢查貼膠可能的抗粉刺性及毒性。計劃如果成功，此發酵益生菌貼膠將包含有效量的 SCFAs 可抑制 P. acnes 在青春痘的過度生長。 ;Dysbiotic acne vulgaris is defined as microbial imbalance with the over-growth of Propionibacterium acnes (P. acnes) in the human acne microbiome. Results in our previous publications clearly demonstrated that Staphylococcus epidermidis (S. epidermidis), which co-exists with P. acnes in an acne lesion, can act as a probiotic bacterium. S. epidermidis exploits the carbohydrate fermentation to produce short-chain fatty acids (SCFAs) and rein in the over-growth of P. acnes. However, given that the number of S. epidermidis on acne lesions vary among individuals, the therapeutic effects of topically applied probiotic S. epidermidis bacteria and/or prebiotics may distinctly differ between individuals. To circumvent this variation and produce homogeneously effective acne probiotic patches, we will develop fermented hydrogels by inactivation of probiotic S. epidermidis after bacterial fermentation in hydrogels. The anti-P. acnes properties of SCFAs and other fermented metabolites will be evenly produced in each fermented hydrogel. We will use a mouse model for the granulomatous type of inflammatory acne vulgaris and a cell model of three-dimensional (3D) culture of human sebocytes to validate the efficacy of acne probiotic patches. The effectiveness of fermented hydrogels on suppression of P. acnes growth and reduction of pro-inflammatory interleukin (IL)-6/(MIP-2); IL-8/IL-1β cytokines will be determined using two models above. Three Specific Aims are proposed to verify our hypothesis that fermented hydrogels can uniformly yield the same amounts of SCFAs in acne lesions that harbor different numbers of probiotic bacteria. In Specific Aim 1, we will generate the fermented skin microbiome hydrogels with inactivated probiotic S. epidermidis, and apply the hydrogels onto P. acnes-induced lesions to deliver the effective doses of SCFAs against P. acnes. In Specific Aim 2, we will examine the broad-spectrum capability of fermented hydrogels in growth inhibition of various clinical P. acnes strains, and explore the effectiveness of fermented hydrogels for reduction of P. acnes-induced inflammation. In Specific Aim 3, we will compare the anti-P. acnes activities of fermented hydrogels with individual SCFA, and investigate the possible anti-comedogenic or toxic activities of fermented hydrogels. When successful, the acne patches will release SCFAs in a dynamic manner, allowing to accumulate the effective doses of SCFAs for suppression of P. acnes growth in an acne microenvironment.
