Skin Microbiome Editing with Fermentation Initiator

Abstract Acne dysbiosis is defined as microbial imbalance with the over growth of Propionibacterium acnes P acnes in the acne microbiome We have demonstrated that Staphylococcus epidermidis S epidermidis a probiotic bacterium co existed with P acnes in an acne lesion can exploit the carbohydrate fermentation to produce short chain fatty acids SCFAs and rein in the over growth of P acnes In collaboration with Surface Bioadvances Inc in San Diego we have developed polyethylene glycol dimethacrylate PEG DMA Lactose monohydrate ALM and propargyl PEG tetra Ac beta D glucose as selective fermentation initiators SFIs which can specifically intensify fermentation activity of S epidermidis but not P acnes In this proposal we will synthesize various PEG carbohydrate conjugates as SFIs and identify the most potent SFI for rebalancing the dysbiotic acne vulgaris The effects of SFIs on the suppression of P acnes growth and reduction of {P acnes induced inflammation} will be investigated We have recently obtained acne biopsies in partnership 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 SFIs on suppression of P acnes growth and reduction of pro inflammatory cytokines will be tested by using ex vivo acne explants Three Specific Aims are proposed to verify our hypothesis In Specific Aim we will compare the differential potencies of PEG macromers and their carbohydrate conjugates as SFIs for S epidermidis and investigate the broad spectrum capability of SFI fermentation in growth inhibition of various clinical P acnes strains In Specific Aim we will determine the efficacy of SFI fermentation for treatment of different inflammatory stages of acne vulgaris {and examine the effect of SFI fermentation on the bacterial abundance in the acne microbiome } In Specific Aim we will {compare the anti P acnes potency of SFIs with SCFAs } and explore the possible anti comedogenic or toxic activities of SFIs We envision that SFIs are able to specifically intensify the probiotic ability of S epidermidis produce SCFAs to beat out its competitor P acnes {The use of SFI to initiate fermentation of probiotic S epidermidis can avoid difficulty in determining how many SCFAs in a mixture can be formulated as anti P acnes agents } When successful the SFI will be {the first fermentation initiator that can edit reshape dysbiotic microbiome without using live microorganisms such as live bacteria or bacteriophages }Project Narratives Both Propionibacterium acnes P acnes and Staphylococcus epidermidis S epidermidis co exist within acne lesions These two bacteria may compete with each other for the carbon sources of fermentation Our strategy here is to exclusively trigger the fermentation of S epidermidis using polyethylene glycol PEG macromers as selective fermentation initiators SFIs to specifically amplify the probiotic activity of S epidermidis against P acnes