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Abstract
Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis.
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1 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Bacteriology and Immunology, Medicum, University of Helsinki, Helsinki, Finland
2 Department of Informatics, Faculty of Natural and Mathematical Sciences, King’s College London, London, UK; Cutaneous Medicine Unit, St. John’s Institute of Dermatology and Biomedical Research Centre, Faculty of Life Sciences and Medicine, King’s College London, London, UK
3 Centre for Translational Microbiome Research (CTMR), Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
4 Institut Curie, Paris, France; INSERM, U900, Paris, France; Mines ParisTech, Fontainebleau, France; INSERM, U932, Paris, France
5 Department of Dermatology, University Hospital Duesseldorf, Duesseldorf, Germany; Department of Dermatology, Venereology and Oncodermatology, University of Pécs, Pécs, Hungary
6 Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
7 Department of Dermatology, University Hospital Duesseldorf, Duesseldorf, Germany
8 Department of Cell and Molecular Biology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden
9 Department of Dermatology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands
10 Institute for Medical Microbiology and Hospital Hygiene, Heinrich Heine University Duesseldorf, Duesseldorf, Germany
11 St John’s Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, Kings College London, London, UK
12 Cutaneous Medicine Unit, St. John’s Institute of Dermatology and Biomedical Research Centre, Faculty of Life Sciences and Medicine, King’s College London, London, UK
13 Department of Dermatology, Allergology and Venereology, University of Helsinki and Helsinki University Hospital, Inflammation Centre, Helsinki, Finland
14 Pharmacology Unit, School of Pharmacy, The Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
15 Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany
16 Department of Bacteriology and Immunology, Medicum, University of Helsinki, Helsinki, Finland
17 Department of Informatics, Faculty of Natural and Mathematical Sciences, King’s College London, London, UK
18 Fios Genomics, Edinburgh, UK
19 Institut Curie, Paris, France; INSERM, U900, Paris, France; Mines ParisTech, Fontainebleau, France; CNRS, UMR144, Paris, France
20 Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland; Institute of Biomedical Technology, University of Tampere, Tampere, Finland; Institute of Biotechnology, University of Helsinki, Helsinki, Finland
21 Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; School of Basic and Medical Biosciences, King’s College London, London, UK
22 Institut Curie, Paris, France; INSERM, U932, Paris, France