Antibiotics without selectivity may destroy the friendly microbes in the human microbiome that helps fight pathogens and maintain homeostasis of microbiome. The fermentation product (yogurt) of friendly bacteria in human intestine promotes a healthy digestive system. With several publications, our group has for the first time demonstrated a skin probiotic approach for treatment of acne vulgaris. We hypothesize that dysbiosis in the acne microbiome can be re-balance by the skin probiotic bacteria. Results in our previous publication indicated that Staphylococcus epidermidis (S. epidermidis), a skin bacterium, can fermentatively metabolize the glycerol to short-chain fatty acids (SCFAs) which suppress the growth of Propionibacterium acnes (P. acnes), an opportunistic bacterium highly associated with acne vulgaris. Although S. epidermidis has fermentation activity, the bacteria represent one of causative agents involved with infections of many types of indwelling medical devices in hospital. Thus, we are here seeking a S. epidermidis alternative bacterium which can effectively rein in the over-growth of P. acnes as well as mitigate the P. acnes-induced inflammation.In this collaborative proposal, we will team up with Grape-King Inc. at Taoyuan, Taiwan to develop acne probiotics. The acne probiotics will be generated by fermentation of skin microorganisms in glycerol. In Specific Aim 1, we will identify the probiotic microorganisms from the human skin microbiome for the development of acne probiotics, and investigate the inhibitory effects of acne probiotics against various clinical P. acnes strains. In Specific Aim 2, we will profile the SCFAs in the ferment metabolites of probiotic microorganisms using NMR spectrometers, select the most potent SCFA as an anti-P. acnes agent, and evaluate the bactericidal activities of acne probiotics against P. acnes in vivo. In Specific Aim 3, we will assess the possible perturbation effects of acne probiotics on skin commensals, and examine the cytotoxicities of acne probiotics.Besides yogurt, microbial fermentation has been widely employed in the development of various products including wine and vinegar. Each fermentation industry can get annual profits of over $100 million. A potent microorganism strain that can interfere with the growth of P. acnes via fermentation will be identified for a Skin Microbiome Bank established at Pi’s lab at National Central University for development of acne probiotics. In this two-year proposal, we will validate the anti-P. acnes efficacy of probiotic bacteria and SCFAs in vitro and in vivo. When successful, an acne probiotic containing at least three products [probiotic bacteria, glycerol as a fermentation substrate, and SCFAs) will be obtained for treatment of acne vulgaris.