Targeting the Cutaneous Microbiota in Atopic Dermatitis by Coal Tar via AHR-Dependent Induction of Antimicrobial Peptides

J Invest Dermatol. 2020 Feb;140(2):415-424.e10. doi: 10.1016/j.jid.2019.06.142. Epub 2019 Jul 22.


Skin colonization by Staphylococcus aureus and its relative abundance is associated with atopic dermatitis (AD) disease severity and treatment response. Low levels of antimicrobial peptides in AD skin may be related to the microbial dysbiosis. Therapeutic targeting of the skin microbiome and antimicrobial peptide expression can, therefore, restore skin homeostasis and combat AD. In this study, we analyzed the cutaneous microbiome composition in 7 patients with AD and 10 healthy volunteers upon topical coal tar or vehicle treatment. We implemented and validated a Staphylococcus-specific single-locus sequence typing approach combined with classic 16S ribosomal RNA marker gene sequencing to study the bacterial composition. During coal tar treatment, Staphylococcus abundance decreased, and Propionibacterium abundance increased, suggesting a shift of the microbiota composition toward that of healthy controls. We, furthermore, identified a hitherto unknown therapeutic mode of action of coal tar, namely the induction of keratinocyte-derived antimicrobial peptides via activation of the aryl hydrocarbon receptor. Restoring antimicrobial peptide levels in AD skin via aryl hydrocarbon receptor-dependent transcription regulation can be beneficial by creating a (anti)microbial milieu that is less prone to infection and inflammation. This underscores the importance of coal tar in the therapeutic aryl hydrocarbon receptor armamentarium and highlights the aryl hydrocarbon receptor as a target for drug development.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Anti-Infective Agents / pharmacology*
  • Anti-Infective Agents / therapeutic use
  • Antimicrobial Cationic Peptides / immunology
  • Antimicrobial Cationic Peptides / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / agonists*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biopsy
  • Cell Line
  • Coal Tar / pharmacology*
  • Coal Tar / therapeutic use
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / microbiology
  • Dermatitis, Atopic / pathology
  • Dysbiosis / drug therapy*
  • Dysbiosis / immunology
  • Dysbiosis / microbiology
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Gene Knockdown Techniques
  • Healthy Volunteers
  • Humans
  • Keratinocytes
  • Male
  • Microbiota / drug effects*
  • Microbiota / immunology
  • Middle Aged
  • Primary Cell Culture
  • Propionibacterium / immunology
  • Propionibacterium / isolation & purification
  • Receptors, Aryl Hydrocarbon / agonists*
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism
  • Skin / drug effects
  • Skin / immunology
  • Skin / microbiology*
  • Skin / pathology
  • Skin Cream / pharmacology
  • Skin Cream / therapeutic use
  • Staphylococcus aureus / immunology
  • Staphylococcus aureus / isolation & purification
  • Young Adult


  • AHR protein, human
  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Basic Helix-Loop-Helix Transcription Factors
  • Receptors, Aryl Hydrocarbon
  • Coal Tar