Dupilumab but not cyclosporine treatment shifts the microbiome toward a healthy skin flora in patients with moderate-to-severe atopic dermatitis


Jan Hartmann, Lucas Moitinho-Silva, Nicole Sander, Inken Harder, Robert Häsler, Elke Rodriguez, Eva Haufe, Andreas Kleinheinz, Susanne Abraham, Annice Heratizadeh, Elke Weisshaar, Knut Schäkel, Christiane Handrick, Matthias Augustin, Andreas Wollenberg, Petra Staubach-Renz, Konstantin Ertner, Michael Sticherling, Beate Schwarz, Sven Quist, Franca Wiemers, Florian Schenck, Julia Wildberger, Lukas Tittmann, Wolfgang Lieb, Jochen Schmitt, Thomas Werfel, Stephan Weidinger








BACKGROUND: Atopic dermatitis (AD) patients display an altered skin microbiome which may not only be an indicator but also a driver of inflammation. We aimed to investigate associations among AD patients‘ skin microbiome, clinical data, and response to systemic therapy in patients of the TREATgermany registry. METHODS: Skin swabs of 157 patients were profiled with 16S rRNA gene amplicon sequencing before and after 3 months of treatment with dupilumab or cyclosporine. For comparison, 16s microbiome data from 258 population-based healthy controls were used. Disease severity was assessed using established instruments such as the Eczema Area and Severity Index (EASI). RESULTS: We confirmed the previously shown correlation of Staphylococcus aureus abundance and bacterial alpha diversity with AD severity as measured by EASI. Therapy with Dupilumab shifted the bacterial community toward the pattern seen in healthy controls. The relative abundance of Staphylococci and in particular S. aureus significantly decreased on both lesional and non-lesional skin, whereas the abundance of Staphylococcus hominis increased. These changes were largely independent from the degree of clinical improvement and were not observed for cyclosporine. CONCLUSIONS: Systemic treatment with dupilumab but not cyclosporine tends to restore a healthy skin microbiome largely independent of the clinical response indicating potential effects of IL-4RA blockade on the microbiome.