Dysbiotic Rebalancing with S. epidermidis Fermentation in Acne Vulgaris

Huang, Chun-Ming

Abstract

Dysbiosis refers to a condition with microbial imbalances within the human microbiome. Yogurts are the best examples of using fermenting gut bacteria to rebalance the gut dysbiosis. Our results demonstrate for the first time that Staphylococcus epidermidis (S. epidermidis), a commensal bacterium of the human skin, functions as a probiotic microorganism that employs fermentation to restrain the over- growth of Propionibacterium acnes, a skin opportunistic bacterium associated with acne vulgaris. Like microbial competition in a ripening fruit, we envision that S. epidermidis and P. acnes within an acne microenvironment compete with each other for the same carbon source of fermentation. To intensify the ability of S. epidermidis to beat out its competitor (P. acnes), the a-lactose monohydrate (ALM), a selective fermentation initiator, will be used to exclusively trigger the fermentation of S. epidermidis. The concept of using S. epidermidis fermentation against P. acnes will be applied for {development of post-antibiotic adjuvant therapy for treatment of acne vulgairs. A short-chain fatty acid (SCFA) with antimicrobial activity in the fermentative metabolites of S. epidermidis will be formulated with clindamycin, a commonly prescribed topical antibiotic for acne vulgaris. The effects of SCFA on the suppression of P. acnes growth and reduction of required doses of clindamycin will be investigated. {We have recently obtained acne biopsies in collaboration 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 SCFA or the SCFA/clindamycin combination 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 validate our hypothesis.
In Specific Aim 1, we will identify a SCFA for selectively eliminating P. acnes without inhibiting S. epidermidis, {measure the concentrations of SCFAs in human ex vivo acne explants and, determine an effective concentration of SCFA for suppression of P. acnes growth.
In Specific Aim 2, we will validate the essential role of probiotic S. epidermidis in the inhibitio of P. acnes growth in acne lesions, compare the potency of SCFA against P. acnes to that of antibiotic, and develop SCFA as an antibiotic adjuvant.
In Specific Aim 3, we will explore the possible disruptive effects of SCFA on skin commensals, and examine the cytotoxicities of SCFA with/without clindamycin to skin cells.} In addition to developing a novel acne therapeutic {(SCFA as post-antibiotic adjuvant therapy)}, we emphasize the notion that {combination of antibiotics with probiotic-derived metabolites may greatly reduce the side-effects of antibiotics for treatment of acne vulgaris.}

Public Health Relevance

Dysbiotic acne vulgaris is associated with the over-growth of Propionibacterium acnes (P. acnes). Our results have demonstrated that Staphylococcus epidermidis (S. epidermidis), a Gram-positive bacterium co-existed with P. acnes in an acne lesion, can exploit the carbohydrate fermentation to inhibit the growth of P. acnes. Our approach here is to selectively amplify the fermentation activity of S. epidermidis to rebalance the acne dysbiosis {and develop short-chain fatty acids, main ferment metabolites, as post- antibiotic adjuvant therapy for treatment of acne vulgaris.}