Staphylococcus epidermidis (S. epidermidis), a skin probiotic bacterium, coexisted with Propionibacterium acnes (P. acnes) in an acne lesion in human.Microbial imbalance with the over-growth of P. acnes in the acne microbiome istermed “acne dysbiosis”. Results in our publication have demonstrated that S.epidermidis can mediate the carbohydrate fermentation to yield short-chain fattyacids (SCFAs) and rein in the over-growth of P. acnes. The rebalance of the acnedysbiosis 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. Theanalogs of SCFAs derived from metabolites of S. epidermidis fermentation will beused as antibiotic adjuvants and applied for development of post-antibioticadjuvant therapy for treatment of acne vulgaris.Three Specific Aims are proposed to validate the anti-P. acnes potency of SCFAanalogs as antibiotic adjuvants. In Specific Aim 1, we identify short-chain fattyacid (SCFAs) produced by α-Lactose monohydrate (ALM) fermentation of S.epidermidis for selectively eliminating P. acnes, and determine the effects ofSCFAs on the growth of major skin commensals. In Specific Aim 2, we willsynthesize the SCFA analogs for suppression of P. acnes growth, and determinethe of skin innate immunity by epicutaneous application of analogs of SCFAs. InSpecific Aim 3, we will develop SCFA analogs as adjuvants for post-antibioticadjuvant therapy, and explore the possible influence on the hemostasis of skinmicrobiome and activities of skin cells. The SCFA analogs will be developed as“antibiotic adjuvants” and tested their ability to reduce the effective dose of topicalantibiotics for acne treatment, and minimize the non-specific killing effect ofantibiotics on skin commensals. When successful, the SCFA analogs will be thefirst antibiotic adjuvant that is designed based on natural strategy (fermentation)of human skin commensals.