Deficiency of Short-Chain Fatty Acids in Acne Vulgaris

摘要 我们发表的结果首次证明表皮葡萄球菌（S。 表皮葡萄球菌），一种人类皮肤的细菌，作为益生菌发挥作用， 碳水化合物发酵，抑制痤疮丙酸杆菌的过度生长， 与寻常痤疮有关的细菌。强化S. epidermidis击败竞争对手 (P.痤疮），α-乳糖一水合物（ALM），一种选择性发酵引发剂，已被用于 专门引发S.表皮由ALM产生的短链脂肪酸（SCFA） S.在体外和小鼠中，表皮松解物有效地抑制痤疮丙酸杆菌的生长。我们因此 假设痤疮病变内的SCFA是控制过度生长的痤疮丙酸杆菌的关键组分。的 人皮肤中SCFA的缺乏可促进寻常痤疮的进展。 SCFA将在抗生素后辅助治疗中作为佐剂用于治疗寻常痤疮。 抗生素后辅助治疗可减少抗生素的用量和副作用。我们有 最近与蒂萨R. Hata，皮肤科主任 加州大学圣地亚哥分校（UCSD）的临床试验部门。这些痤疮活检已经被用来 建立离体痤疮外植体。SCFA或SCFA/抗生素组合对 将通过使用例如， 体内痤疮外植体。此外，我们还将探讨SCFAs对降低细胞凋亡的作用机制。 通过抑制组蛋白脱乙酰酶（HDAC）治疗炎性寻常痤疮。 提出了三个具体目标来验证我们的假设。在具体目标1中，我们将获得 P.痤疮选择性SCFAs，并检查HDAC的抑制作用SCFAs在减少P。 痤疮引起的炎症在具体目标2中，我们将探讨SCFAs在 使用SCFA缺陷/无菌小鼠抑制痤疮丙酸杆菌生长，并定量 来源于不同阶段的寻常痤疮的人离体痤疮外植体中的SCFA。在具体目标3中， 我们将使用人离体痤疮外植体来评价使用 抗生素和SCFA或ALM的组合，并检测可能的抗粉刺和毒性活性 的SCFA。 我们在这里介绍一个新的概念，益生菌在痤疮病变表达碳水化合物 发酵并产生SCFAs以重新平衡痤疮生态失调。如果成功，SCFA自然 由人类微生物组中的细菌产生的抗生素可用作抗生素佐剂， 治疗各种人类感染。

Abstract Results in our publication demonstrate for the first time that Staphylococcus epidermidis (S. epidermidis), a commensal bacterium of the human skin, functions as a probiotic bacterium that employs carbohydrate fermentation to restrain the over-growth of Propionibacterium acnes, a skin opportunistic bacterium associated with acne vulgaris. To intensify the ability of S. epidermidis to beat out its competitor (P. acnes), the α-lactose monohydrate (ALM), a selective fermentation initiator, has been used to exclusively trigger the fermentation of S. epidermidis. Short-chain fatty acids (SCFAs) produced by ALM fermentation of S. epidermidis effectively suppress the growth of P. acnes in vitro and in mice. We thus hypothesize that SCFAs within acne lesions are key components to rein in the overgrown P. acnes. The deficiency of SCFAs in human skin may promote the progression of acne vulgaris. SCFAs will act as adjuvants in the post-antibiotic adjuvant therapy for treatment of acne vulgaris. The post-antibiotic adjuvant therapy will reduce the required dose and side-effects of antibiotics. We have recently obtained acne biopsies in collaboration with Dr. Tissa R. Hata, a Director of the Dermatology Clinical Trials Unit at University of California, San Diego (UCSD). These acne biopsies have been used to establish ex vivo acne explants. The effectiveness of SCFA or the SCFA/antibiotic combination on suppression of P. acnes growth and reduction of pro-inflammatory cytokines will be evaluated by using ex vivo acne explants. Furthermore, we will explore the action mechanism of SCFAs on reduction of inflammatory acne vulgaris via inhibition of histone deacetylase (HDAC). Three Specific Aims are proposed to validate our hypothesis. In Specific Aim 1, we will obtain the P. acnes-selective SCFAs, and examine the role of the inhibition of HDAC by SCFAs in the reduction of P. acnes-induced inflammation. In Specific Aim 2, we will explore the essential roles of SCFAs in the inhibition of P. acnes growth using SCFA-deficient/germ-free mice, and quantify the concentrations of SCFAs in human ex vivo acne explants derived from different stages of acne vulgaris. In Specific Aim 3, we will {use the human ex vivo acne explants to evaluate the post-antibiotic adjuvant therapy using the combination of antibiotic and SCFA or ALM, and detect the possible anti-comedogenic and toxic activities of SCFAs.} We here introduce a new concept that probiotic bacteria within acne lesions express carbohydrate fermentation and produce the SCFAs to rebalance the acne dysbiosis. If successfully, SCFAs naturally produced by commensal bacteria in the human microbiome can be used as antibiotic adjuvants for treatment of various human infections.