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