Antibiotics without selectivity may destroy the friendly microbes in the human microbiomethat helps fight pathogens and maintain homeostasis of microbiome. The fermentation product(yogurt) of friendly bacteria in human intestine promotes a healthy digestive system. With severalpublications, our group has for the first time demonstrated a skin probiotic approach for treatmentof acne vulgaris. We hypothesize that dysbiosis in the acne microbiome can be re-balance by theskin probiotic bacteria. Results in our previous publication indicated that Staphylococcusepidermidis (S. epidermidis), a skin bacterium, can fermentatively metabolize the glycerol to shortchainfatty acids (SCFAs) which suppress the growth of Propionibacterium acnes (P. acnes), anopportunistic bacterium highly associated with acne vulgaris. Although S. epidermidis hasfermentation activity, the bacteria represent one of causative agents involved with infections ofmany types of indwelling medical devices in hospital. Thus, we are here seeking a S. epidermidisalternative bacterium which can effectively rein in the over-growth of P. acnes as well as mitigatethe P. acnes-induced inflammation.In this collaborative proposal, we will team up with Grape-King Inc. at Taoyuan, Taiwan todevelop acne probiotics. The acne probiotics will be generated by fermentation of skinmicroorganisms in glycerol. In Specific Aim 1, we will identify the probiotic microorganisms fromthe human skin microbiome for the development of acne probiotics, and investigate the inhibitoryeffects of acne probiotics against various clinical P. acnes strains. In Specific Aim 2, we will profilethe 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 ofacne probiotics against P. acnes in vivo. In Specific Aim 3, we will assess the possible perturbationeffects of acne probiotics on skin commensals, and examine the cytotoxicities of acne probiotics.Besides yogurt, microbial fermentation has been widely employed in the development ofvarious products including wine and vinegar. Each fermentation industry can get annual profits ofover $100 million. A potent microorganism strain that can interfere with the growth of P. acnes viafermentation will be identified for a Skin Microbiome Bank established at PI’s lab at NationalCentral University for development of acne probiotics. In this two-year proposal, we will validatethe 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 fermentationsubstrate, and SCFAs) will be obtained for treatment of acne vulgaris.