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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)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Darier’s Disease ; Genodermatosis ; Malodour ; Microbiome ; Skin Barrier ; Transcriptome; Atopic-dermatitis; Protease Inhibitor; Axilla Secretions; Skin Microbiome; Psoriasis; Proteins
ISSN (print) / ISBN 2049-2618
e-ISSN 2049-2618
Zeitschrift Microbiome
Quellenangaben Band: 11, Heft: 1, Seiten: , Artikelnummer: 162 Supplement: ,
Verlag BioMed Central
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Comparative Microbiome Analysis (COMI)
Institute of Computational Biology (ICB)
Institute for Allergy Research (IAF)
Förderungen European Research Council (ERC)
Eva Luise and Horst Koehler Stiftung (ELHKS)
La Roche Posay Research grant
National Research Center for Environmental Health GmbH
Helmholtz Zentrum Muenchen
Heisenberg professorship
ERC grant "IMCIS"
Deutsche Forschungsgemeinschaft
Projekt DEAL