Abstract
Background: The skin microbiome plays a crucial role in defending against pathogens and modulating immunity, and its dysregulation is linked to various skin conditions, including acne. Methods: In this study, four previously identified strains-Staphylococcus epidermidis B424F-5, S. epidermidis BS47C-1, Dermacoccus profundi BS35F-3, and Streptococcus salivarius BS320F-4- were selected from a skin microbiome database of healthy individuals. The efficacy and safety of these strains against acne-related inflammation were evaluated using in vitro and in vivo animal model experiments. Results: Cutibacterium acnes exposure increased the expression of acne-associated inflammatory mediators-such as IL-1β, IL-6, IL-8, COX-2, iNOS, and TNF-α-particularly in keratinocytes, without inducing cytotoxicity. Treatment with heat-killed S. epidermidis BS47C-1 (SE2), D. profundi BS35F-3 (DP), and S. salivarius BS320F-4 (SS) significantly reduced these markers in vitro. In vivo, topical application of the strains alleviated inflammation in a C. acnes-induced mouse model, with histological evidence of reduced erythema and immune cell infiltration. Bulk RNA sequencing of keratinocytes showed that SE2 and DP downregulated cytokine and interferon signaling while enhancing skin barrier and antimicrobial gene expression, suggesting a dual anti-inflammatory and barrier-supporting mechanism. Conclusion: These results provide compelling evidence of the efficacy and safety of human skin microbiome-derived strains as potential topical treatments for acne. By targeting both microbial colonization and inflammatory pathways, these strains offer a promising avenue for the development of novel acne therapeutics.