Aidan O'Hara

The skin microbiome is a diverse ecosystem, consisting of bacteria, viruses, and eukaryotic microorganisms. Prior research has shown that the metabolites that bacterial skin commensals produce are key mediators of virulence control within the bacterial skin microbiome. Despite the importance of the metabolites in this role, the role that these metabolites possess in affecting host responses is largely unknown. Studies have shown that bacterial skin metabolites are able to modulate host antimicrobial peptide (AMP) production at the skin’s barrier. AMPs are small, cationic peptides that typically mediate bactericidal effects through bacterial membrane destabilization. It’s unknown what ecological consequences the increased AMP production has on the composition of the skin microbiome. It’s well established that altered skin microbiome compositions and AMP production are drivers of inflammatory skin disorders, such as atopic dermatitis and psoriasis. Therefore, unraveling the complex interactions occurring between increased AMP production and the bacterial skin microbiome’s composition is clinically relevant for understanding the progression and development of atopic dermatitis and psoriasis. Additionally, the broader immunological developments occurring in response to the bacterial skin metabolome have not been investigated thoroughly. To investigate these observations, I will be 1) determining the ubiquity of AMP induction among bacterial skin commensal metabolites and the ecological consequences of the induction, 2) understanding the range of cytokines and AMPs induced by bacterial skin commensal metabolites, and 3) investigating the translational relevance of the in vitro findings in an in vivo mouse model. Findings from my research are expected to reveal a mechanism by which the skin barrier maintains functionality and proper skin microbiome composition.