表皮葡萄球菌，一種皮膚益生菌，和痤瘡桿菌共同存在於人類因痤瘡所產生的傷口。而痤瘡微生物相因痤瘡桿菌的過度生長所造成的微生物失衡，稱為痤瘡菌叢不良。我們先前的研究結果指出，表皮葡萄球菌可利用碳水化合物進行發酵，產生短鏈脂肪酸(short-chain fatty acids, SCFAs)，並控制痤瘡桿菌的過度生長。選擇性地放大表皮葡萄球菌的發酵活性可以達成痤瘡菌叢不良的再平衡。α-乳糖單水合物，一種選擇性的發酵起始劑，被專門用來觸發表皮葡萄球菌的發酵。自表皮葡萄球菌的代謝物中所衍生的SCFAs類似物，將被用來當作抗生素治療痤瘡的佐劑，並應用於發展經抗生素治療後的輔助治療本研究將包含三個目標，目的在找出具輔助抗生素治療痤瘡桿菌過度生長之潛力的SCFAs類似物。第一個目的，我們將找出經表皮葡萄球菌利用α-乳糖單水合物，而生成具選擇性抑制痤瘡桿菌生長潛力的SCFAs類似物，並探討這些SCFAs類似物對皮膚主要共生菌叢的影響。第二個目的，我們將合成SCFAs類似物來抑制痤瘡桿菌的生長，並研究，經表皮利用這些SCFAs類似物後，對皮膚先天免疫的改變。第三個目的，我們將發展SCFAs類似物作為抗生素佐劑，並測試它們降低外用抗生素治療痤瘡的有效劑量的能力，以最小化抗生素對皮膚共生菌叢的非專一性殺滅效果。若我們可以成功地找出上述的SCFAs類似物，這將會是第一個經由人類皮膚共生菌叢發酵所產生的天然抗生素佐劑。 ;Staphylococcus epidermidis (S. epidermidis), a skin probiotic bacterium, co-existed with Propionibacterium acnes (P. acnes) in an acne lesion in human. Microbial imbalance with the over-growth of P. acnes in the acne microbiome is termed “acne dysbiosis”. Results in our publication have demonstrated that S. epidermidis can mediate the carbohydrate fermentation to yield short-chain fatty acids (SCFAs) and rein in the over-growth of P. acnes. The rebalance of the acne dysbiosis can be achieved by selectively amplifying the fermentation activity of S. epidermidis. The α-lactose monohydrate (ALM), a selective fermentation initiator (SFI), was used to exclusively trigger the fermentation of S. epidermidis. The analogs of SCFAs derived from metabolites of S. epidermidis fermentation will be used as antibiotic adjuvants and applied for development of post-antibiotic adjuvant therapy for treatment of acne vulgaris. Three Specific Aims are proposed to validate the anti-P. acnes potency of SCFA analogs as antibiotic adjuvants. In Specific Aim 1, we identify short-chain fatty acid (SCFAs) produced by α-Lactose monohydrate (ALM) fermentation of S. epidermidis for selectively eliminating P. acnes, and determine the effects of SCFAs on the growth of major skin commensals. In Specific Aim 2, we will synthesize the SCFA analogs for suppression of P. acnes growth, and determine the of skin innate immunity by epicutaneous application of analogs of SCFAs. In Specific Aim 3, we will develop SCFA analogs as adjuvants for post-antibiotic adjuvant therapy, and explore the possible influence on the hemostasis of skin microbiome and activities of skin cells. The SCFA analogs will be developed as “antibiotic adjuvants” and tested their ability to reduce the effective dose of topical antibiotics for acne treatment, and minimize the non-specific killing effect of antibiotics on skin commensals. When successful, the SCFA analogs will be the first antibiotic adjuvant that is designed based on natural strategy (fermentation) of human skin commensals.
