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Amar, Y.* ; Rogner, D.* ; Silva, R.* ; Fösel, B. ; Ud-Dean, M. ; Lagkouvardos, I.* ; Steimle-Grauer, S.A.* ; Niedermeier, S.* ; Kublik, S. ; Jargosch, M.* ; Heinig, M. ; Thomas, J. ; Eyerich, S. ; Wikström, J.D.* ; Schloter, M. ; Eyerich, K.* ; Biedermann, T.* ; Köberle, M.*

Darier's disease exhibits a unique cutaneous microbial dysbiosis associated with inflammation and body malodour.

Microbiome 11:162 (2023)

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BACKGROUND: Darier's disease (DD) is a genodermatosis caused by mutations of the ATP2A2 gene leading to disrupted keratinocyte adhesion. Recurrent episodes of skin inflammation and infections with a typical malodour in DD indicate a role for microbial dysbiosis. Here, for the first time, we investigated the DD skin microbiome using a metabarcoding approach of 115 skin swabs from 14 patients and 14 healthy volunteers. Furthermore, we analyzed its changes in the context of DD malodour and the cutaneous DD transcriptome. RESULTS: We identified a disease-specific cutaneous microbiome with a loss of microbial diversity and of potentially beneficial commensals. Expansion of inflammation-associated microbes such as Staphylococcus aureus and Staphylococcus warneri strongly correlated with disease severity. DD dysbiosis was further characterized by abundant species belonging to Corynebacteria, Staphylococci and Streptococci groups displaying strong associations with malodour intensity. Transcriptome analyses showed marked upregulation of epidermal repair, inflammatory and immune defence pathways reflecting epithelial and immune response mechanisms to DD dysbiotic microbiome. In contrast, barrier genes including claudin-4 and cadherin-4 were downregulated. CONCLUSIONS: These findings allow a better understanding of Darier exacerbations, highlighting the role of cutaneous dysbiosis in DD inflammation and associated malodour. Our data also suggest potential biomarkers and targets of intervention for DD. Video Abstract.

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