Results in our publication demonstrate for the first time that Staphylococcus epidermidis (S. epidermidis), a commensal bacterium of the human skin, functions as a probiotic bacterium that employs carbohydrate fermentation to restrain the over-growth of Propionibacterium acnes, a skin opportunistic bacterium associated with acne vulgaris. To intensify the ability of S. epidermidis to beat out its competitor (P. acnes), the ?-lactose monohydrate (ALM), a selective fermentation initiator, has been used to exclusively trigger the fermentation of S. epidermidis. Short-chain fatty acids (SCFAs) produced by ALM fermentation of S. epidermidis effectively suppress the growth of P. acnes in vitro and in mice. We thus hypothesize that SCFAs within acne lesions are key components to rein in the overgrown P. acnes. The deficiency of SCFAs in human skin may promote the progression of acne vulgaris. SCFAs will act as adjuvants in the post-antibiotic adjuvant therapy for treatment of acne vulgaris. The post-antibiotic adjuvant therapy will reduce the required dose and side-effects of antibiotics. 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/antibiotic combination on suppression of P. acnes growth and reduction of pro-inflammatory cytokines will be evaluated by using ex vivo acne explants. Furthermore, we will explore the action mechanism of SCFAs on reduction of inflammatory acne vulgaris via inhibition of histone deacetylase (HDAC).
Three Specific Aims are proposed to validate our hypothesis.
In Specific Aim 1, we will obtain the P. acnes-selective SCFAs, and examine the role of the inhibition of HDAC by SCFAs in the reduction of P. acnes-induced inflammation.
In Specific Aim 2, we will explore the essential roles of SCFAs in the inhibition of P. acnes growth using SCFA-deficient/germ-free mice, and quantify the concentrations of SCFAs in human ex vivo acne explants derived from different stages of acne vulgaris.
In Specific Aim 3, we will {use the human ex vivo acne explants to evaluate the post-antibiotic adjuvant therapy using the combination of antibiotic and SCFA or ALM, and detect the possible anti-comedogenic and toxic activities of SCFAs.} We here introduce a new concept that probiotic bacteria within acne lesions express carbohydrate fermentation and produce the SCFAs to rebalance the acne dysbiosis. If successfully, SCFAs naturally produced by commensal bacteria in the human microbiome can be used as antibiotic adjuvants for treatment of various human infections.

Public Health Relevance

s Our results demonstrate that Staphylococcus epidermidis (S. epidermidis) can exploit the carbohydrate fermentation to produce short-chain fatty acids (SCFAs) which exert antimicrobial activities against Propionibacterium acnes (P. acnes), a bacterium highly associated with acne vulgaris. We envision that SCFA deficiency in acne lesions is the leading cause of progression of acne vulgaris. SCFAs will be used as adjuvants for post antibiotic therapy for acne treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AR069745-02
Application #
9468328
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Cibotti, Ricardo
Project Start
2017-04-07
Project End
2018-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Dermatology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093