Editors' ChoiceDERMATITIS

Scratching the surface: Alterations of skin microbiota in the initiation of eczematous dermatitis

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Science Translational Medicine  20 May 2015:
Vol. 7, Issue 288, pp. 288ec82
DOI: 10.1126/scitranslmed.aac499

Alterations in the microbiome have been implicated in many diseases, including inflammatory skin disease. Despite a well-documented association of dysbiosis in atopic dermatitis, the chicken-or-egg relationship of dysbiosis and inflammatory skin disease has not been determined. To address this issue, Kobayashi and colleagues employ a mouse model using A disintegrin and metalloproteinase 17 (ADAM17)–deficient mice (Adam17fl/flSox9-Cre) in which microbiota alterations and disease expression mimic human atopic dermatitis. The authors assess differences in the microbiota and how specific altered bacteria (Staphylococcus aureus and Corynebacterium bovis) affect immune dysregulation and initiation of inflammation.

Here, the authors discovered that Adam17fl/flSox9-Cre mice exhibited eczematous lesions with lymphocytic and mast cell infiltration, increased barrier dysfunction, and increased serum IgE and Th2 cytokines, mimicking human atopic dermatitis. Compared with wild-type littermates, these mice exhibited significantly decreased skin bacterial diversity and emergence of S. aureus and C. bovis. Microbial differences were detected prior to the emergence of dermatitis, and treatment of the drinking water with antibiotics abrogated the development of skin inflammation. This suggests that alterations in the microbiota were causal in the development of inflammation. In mice with established disease, antibiotic treatment reduced serum concentrations of the inflammatory cytokines interleukin (IL)-1β, IL-6, IL-13, IL-17A, and IL-17F and reversed the dysbiosis. The authors showed that S. aureus alone was sufficient to elicit disease, but only if the host had preexisting epidermal dysfunction (Adam17 or FLG mutation). This suggests that a defective barrier may be required to allow persistent colonization with these bacteria and indicates an important of the host in this process.

Together, these data suggest that dysbiosis occurs first and plays an important role in the initiation of inflammation with an altered epidermal barrier. The association of S. aureus in atopic dermatitis and other atopic diseases is well documented, but this paper is the first to illustrate that dysbiosis precedes disease expression in a mouse model. This work provides exciting insight into how humans with barrier dysfunction may acquire microbial differences leading to inflammation.

T. Kobayashi et al., Dysbiosis and Staphyloccus aureus colonization drives inflammation in atopic dermatitis. Immunity 4, 756–766 (2015). [Abstract]

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