Microbial imbalance with the over-growth of Propionibacterium acnes (P. acnes) in the acnemicrobiome is termed “acne dysbiosis”. We have demonstrated that Staphylococcus epidermidis (S.epidermidis), a probiotic bacterium co-existed with P. acnes in an acne lesion, can exploit thecarbohydrate fermentation to produce short-chain fatty acids (SCFAs) and rein in the over-growthof P. acnes. Our approach here is to selectively amplify the fermentation activity of S. epidermidisto rebalance the acne dysbiosis. The α-lactose monohydrate (ALM), a selective fermentationinitiator (SFI), will be used to exclusively trigger the fermentation of S. epidermidis. The concept ofusing probiotic S. epidermidis against P. acnes will be applied for development of post-antibioticadjuvant therapy for treatment of acne vulgaris. ALM or a SCFA will be formulated withclindamycin, a commonly prescribed topical antibiotic for acne vulgaris. The effects of ALM andSCFA on the suppression of P. acnes growth and reduction of required doses of clindamycin will beinvestigated. The acne biopsies have been used to establish ex vivo acne explants in our laboratory.The effectiveness of probiotic-antibiotic combination on suppression of P. acnes growth andreduction of pro-inflammatory cytokines will be tested by using ex vivo acne explants.Three Specific Aims are proposed to validate our hypothesis. In Specific Aim 1, we identifySCFAs produced by ALM fermentation of S. epidermidis for selectively eliminating P. acnes,quantify the concentrations of SCFAs in acne lesions, and determine the effects of SCFAs on thegrowth of major skin commensals. In Specific Aim 2, we will examine the contribution of histonedeacetylase (HDAC) inhibition by SCFAs to the reduction of P. acnes-induced inflammation invitro and in vivo, and investigate the essential role of free fatty acid receptor 1 (Ffar1) in theanti-inflammatory action of SCFA using Ffar1 knockout mice. In Specific Aim 3, we will detect thedifferential abundance of S. epidermidis and P. acnes in various types/stages of acne lesions,develop ALM/SCFA as adjuvants for post-antibiotic adjuvant therapy, and explore the possibleanti-comedogenic and toxic activities of ALM and SCFA.We envision that ALM is able to specifically intensify the probiotic ability of S. epidermidis,produce SCFAs to “beat” out its competitor (P. acnes), and reduce inflammation via HDACinhibition or Ffar1 activation. The ALM or SCFA will be developed as an “antibiotic adjuvant” andtested its ability to reduce the effective dose of topical antibiotics for acne treatment, and minimizethe non-specific killing effect of antibiotics on skin commensals. When successful, the ALM orSCFA will be the first antibiotic adjuvant that is designed based on natural strategy (fermentation)of human skin commensals.
|Effective start/end date||1/08/16 → 31/07/17|
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):