Fermented Skin Microbiome Acne Patches

Dysbiotic acne vulgaris is defined as microbial imbalance with the over-growth of Propionibacterium acnes (P. acnes) in the human acne microbiome. Results in our previous publications clearly demonstrated that Staphylococcus epidermidis (S. epidermidis), which co-exists with P. acnes in an acne lesion, can act as a probiotic bacterium. S. epidermidis exploits the carbohydrate fermentation to produce short-chain fatty acids (SCFAs) and rein in the over-growth of P. acnes. However, given that the number of S. epidermidis on acne lesions vary among individuals, the therapeutic effects of topically applied probiotic S. epidermidis bacteria and/or prebiotics may distinctly differ between individuals. To circumvent this variation and produce homogeneously effective acne probiotic patches, we will develop fermented hydrogels by inactivation of probiotic S. epidermidis after bacterial fermentation in hydrogels. The anti-P. acnes properties of SCFAs and other fermented metabolites will be evenly produced in each fermented hydrogel. We will use a mouse model for the granulomatous type of inflammatory acne vulgaris and a cell model of three-dimensional (3D) culture of human sebocytes to validate the efficacy of acne probiotic patches. The effectiveness of fermented hydrogels on suppression of P. acnes growth and reduction of pro-inflammatory interleukin (IL)-6/(MIP-2); IL-8/IL-1β cytokines will be determined using two models above. Three Specific Aims are proposed to verify our hypothesis that fermented hydrogels can uniformly yield the same amounts of SCFAs in acne lesions that harbor different numbers of probiotic bacteria. In Specific Aim 1, we will generate the fermented skin microbiome hydrogels with inactivated probiotic S. epidermidis, and apply the hydrogels onto P. acnes-induced lesions to deliver the effective doses of SCFAs against P. acnes. In Specific Aim 2, we will examine the broad-spectrum capability of fermented hydrogels in growth inhibition of various clinical P. acnes strains, and explore the effectiveness of fermented hydrogels for reduction of P. acnes-induced inflammation. In Specific Aim 3, we will compare the anti-P. acnes activities of fermented hydrogels with individual SCFA, and investigate the possible anti-comedogenic or toxic activities of fermented hydrogels. When successful, the acne patches will release SCFAs in a dynamic manner, allowing to accumulate the effective doses of SCFAs for suppression of P. acnes growth in an acne microenvironment.