4.6 Article

Microbial and transcriptional differences elucidate atopic dermatitis heterogeneity across skin sites

Journal

ALLERGY
Volume 76, Issue 4, Pages 1173-1187

Publisher

WILEY
DOI: 10.1111/all.14606

Keywords

atopic dermatitis; inflammation; microbiome

Funding

  1. Knut and Alice Wallenberg Foundation
  2. Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London
  3. King's College Hospital NHS Foundation Trust [guysbrc-2012-1]
  4. Dunhill Medical Trust
  5. Association pour la Recherche contre le Cancer (ARC)
  6. European Research Council [IT-DC 281987]
  7. Institut National de la Sante et de la Recherche Medicale [BIO2012-02, BIO2014-08]
  8. INCA [2011-1-PL BIO-12-IC-1]
  9. Fondation ARSEP [R12023JJ]
  10. ANR [ANR-13-BSV1-0024-02, ANR-10-IDEX-0001-02 PSL*, ANR-11-LABX-0043]
  11. BIOMAP [IMI2-821511]
  12. [261366]

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This study found that different skin sites in atopic dermatitis (AD) patients have microbial heterogeneity, with distinct gene expression profiles between lesional and nonlesional skin. Keratinization dominates the transcriptomic signatures in the posterior thigh, while lipid metabolism is dominant in the upper back.
It is well established that different sites in healthy human skin are colonized by distinct microbial communities due to different physiological conditions. However, few studies have explored microbial heterogeneity between skin sites in diseased skin, such as atopic dermatitis (AD) lesions. To address this issue, we carried out deep analysis of the microbiome and transcriptome in the skin of a large cohort of AD patients and healthy volunteers, comparing two physiologically different sites: upper back and posterior thigh. Microbiome samples and biopsies were obtained from both lesional and nonlesional skin to identify changes related to the disease process. Transcriptome analysis revealed distinct disease-related gene expression profiles depending on anatomical location, with keratinization dominating the transcriptomic signatures in posterior thigh, and lipid metabolism in the upper back. Moreover, we show that relative abundance ofStaphylococcus aureusis associated with disease severity in the posterior thigh, but not in the upper back. Our results suggest that AD may select for similar microbes in different anatomical locations-an AD-like microbiome, but distinct microbial dynamics can still be observed when comparing posterior thigh to upper back. This study highlights the importance of considering the variability across skin sites when studying the development of skin inflammation.

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