Periodic Reporting for period 1 - INTERACT (Skin microbial metabolites and antimicrobial peptides at the interface of skin-gut inflammation)
Reporting period: 2024-03-01 to 2025-08-31
Skin diseases are among the most common health conditions affecting over 900 million people according to the World Health Organization. Skin diseases often co-occur with gut disorders and bidirectional crosstalk along the skin-gut axis influences both gastrointestinal and skin health. Inflammatory skin diseases (ISDs) comprise a series of complex conditions with unknown aetiology, including Psoriasis and Atopic Dermatitis, which accounts for the largest ISD burden. Many ISDs are accompanied by a change in both skin and gut microbiota. Furthermore, antimicrobial peptides that limit bacterial growth are deregulated in ISDs and gut inflammatory disorders such as Inflammatory Bowel Disease. With the support of the Marie Skłodowska-Curie Actions funding, the INTERACT project investigates the impact of gut inflammation and microbial alterations on the skin immunity, through joint research between the Medical University of Vienna and the University of California San Diego. Results obtained in INTERACT will push further the boundaries of our current knowledge in host-microbe interaction and ISD pathophysiology, as well as other feasible gut disorders including Inflammatory Bowel Disease.
Using Dextran Sodium Sulfate (DSS) treatment or oral antibiotic administration, we induced gut inflammation or gut microbial depletion in mice and characterized the skin immune response before and after acute skin inflammation. DSS treatment was followed by topical application of inflammatory triggers, including Imiquimod to induce a Th17-driven response and MC903 to elicit Type 2 inflammation. We analyzed skin parameters such as skin and epidermal thickness and corresponding transcriptomic profiles by RNA sequencing.
Next, metagenomic analyses of stool and skin samples will be performed to characterize bacterial shifts and identify specific gut bacterial species that modulate skin immunity. Furthermore, we aim to define the bacterial secretome as a potential therapeutic target for gut and skin related disorders.
Next, metagenomic analyses of stool and skin samples will be performed to characterize bacterial shifts and identify specific gut bacterial species that modulate skin immunity. Furthermore, we aim to define the bacterial secretome as a potential therapeutic target for gut and skin related disorders.
We found that gut inflammation, using a model of chemically-induced intestinal inflammation, suppresses the skin immune response and this made the skin more vulnerable to Staphylococcus aureus bacterial infection. Interestingly, gut inflammation and antibiotics also dampened skin reactions to inflammatory triggers such as Imiquimod and MC903, and transcriptomic analyses revealed signs of increased glucocorticoid response in the skin. In summary, gut inflammation and microbial changes in the gut suppress skin immunity and increases the susceptibility for skin infections. The next step will be to validate these findings in chronic skin inflammation models, employing genetically engineered mouse models of Psoriasis and Atopic Dermatitis. Furthermore, we will identify the specific bacterial species by metagenomics and their secreted factors that mediate the gut-to-skin connection.