P23 Evaluating the effects of bacterial metabolites on epidermal differentiation in 3D models
Suki Violet Blythe, Matthew CaleyAbstract
Introduction and aims
The skin microbiome is a dynamic community of microorganisms that plays a critical role in maintaining barrier integrity and overall skin health. Cutibacterium acnes, the most prevalent member of the skin microbiome abundant in sebaceous regions contributes to barrier function by metabolizing sebum into free fatty acids in addition to interacting with keratinocytes and immune cells to modulate antimicrobial peptide production and inflammatory responses. The role of individual microbial metabolites in supporting the epidermal differentiation and skin barrier has not been fully elucidated. It is also not yet fully understood how different bacterial species and strains are able to interact with the skin and elicit different effects. A better understanding of the skin microbiome and its metabolites is essential for strategies aimed at preserving barrier function while preventing disease. This project aimed to generate a model for evaluating the effect of relevant bacterial metabolites on epidermal differentiation and the skin barrier.
Methods
Using a combined bioinformatic and lab-based approach, Kyoto Encyclopedia of Genes and Genomes pathways was used to predict potential metabolites produced by C. acnes strains. Combined with a metabolomics approach, where C. acnes strains were grown in artificial sebum to collect metabolites produced in an environment that mimics the sebaceous gland. Metabolites were screened using two-dimensional proliferation and differentiation assays and further investigated in a fully immortalized three-dimensional skin organotypic model.
Results
Bacterial metabolites that altered keratinocyte proliferation, were identified. Investigation of these metabolites identified distinct effects on skin differentiation. Metabolites that decreased proliferation triggered early differentiation with altered patterns of ki67, involucrin, K10 and transglutaminase 1 expression, suggesting a direct role in shaping skin barrier architecture.
Conclusions
These findings highlight the importance of microbial metabolites as active regulators of skin homeostasis and provide a foundation for future research into microbiome-based strategies for enhancing barrier function and preventing skin disorders.