Functional characterization and directed modulation of the skin microbiome in pemphigoid diseases

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The skin microbiota play an increasingly recognized role in immunity and local inflammatory responses, and alternations in these microbial communities are observed in the context of chronic inflammatory skin diseases. During the first funding period we achieved a thorough description of the skin microbiota in the context of bullous pemphigoid (BP) and identified several interesting candidate bacterial taxa that may influence the likelihood of disease emergence and/or severity. In this proposal, we aim to further characterize and test candidate probiotic bacteria and their products for the potential to modulate BP. Accordingly, we plan to achieve a fine-scale taxonomic and functional characterization of the skin microbiome in BP, including functional shotgun metagenomic profiling and experimental evaluation of the identified candidate bacteria in the context of mouse models of pemphigoid disease (PD). Candidate bacterial taxa belonging to the genera Staphylococcus and Propionibacterium are of specific interest, for which short chain fatty acids are candidate bacteria-derived effector molecules modulating disease. The specific aims of our proposal include (i) define species level taxonomy of key candidate indicator species, (ii) determine the effect of candidate probiotic bacteria in a mouse PD model and (iii) identify functional genomic differences and strain level variation in the human BP skin microbiome.