Biofilm Dynamics and Therapeutic Modulation of Skin Microbiota in Sebaceous and Atopic Contexts

Microbial behavior is environmentally dependent and supports the need to study the skin microbiome under conditions as similar to human skin as possible. However, microorganisms are typically grown in nutrient-rich media optimized for growth, which may not accurately represent microbial behavior on the skin. Here, we aimed to add physiological relevance to two models used to study human skin and its microbiome. First, we used a human skin equivalent (HSE) model to evaluate the effects of laminarin and/or a Cutibacterium acnes subspecies defendens strain on atopic dermatitis (AD). We hypothesized that treatment of the model would improve tissue morphology and return AD biomarker expression toward a healthy phenotype. Treatment with C. acnes + laminarin significantly increased stratum corneum thickness and decreased epidermal thickness, more closely resembling the healthy skin phenotype. C. acnes treatment alone partially restored gene expression of AD biomarkers to what is seen in healthy tissues, in addition to decreasing epidermal thickness. Second, we created a more physiologically relevant culture condition to study members of the human skin microbiome and expected to observe differential bacterial behavior between media types. We developed artificial sebum and sweat, which were added to a minimal medium to create our skin-like medium (SC). Skin-resident microbes were cultured in SC medium and compared to standard laboratory medium for growth and biofilm formation. All bacteria tested showed differences between the media in growth, biofilm formation, or both. Co-culture experiments and competitive index calculations of Staphylococcus aureus and C. acnes strain XycW1 revealed the ability of S. aureus to outcompete C. acnes in both planktonic culture and biofilm in SC medium, while C. acnes dominated the biofilm in the mRCM medium. Overall, these data support the importance of environmentally relevant culture conditions and the possible therapeutic use of C. acnes for AD.