Department of Dermatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Dermatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; NIZO, Ede, The Netherlands.
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.
金黄色葡萄球菌的皮肤定植及其相对丰度与特应性皮炎 (AD) 疾病严重程度和治疗反应有关。AD 皮肤中的抗菌肽水平较低可能与微生物失调有关。因此，靶向皮肤微生物组和抗菌肽表达的治疗方法可以恢复皮肤的稳态并对抗 AD。在这项研究中，我们分析了 7 名 AD 患者和 10 名健康志愿者在局部煤焦油或载体治疗后的皮肤微生物组组成。我们实施并验证了一种针对金黄色葡萄球菌的单基因序列分型方法，该方法结合了经典的 16S 核糖体 RNA 标记基因测序，以研究细菌组成。在煤焦油治疗期间，金黄色葡萄球菌的丰度下降，而丙酸杆菌的丰度增加，这表明微生物群组成向健康对照组的转变。此外，我们还确定了煤焦油的一种迄今未知的治疗作用模式，即通过激活芳烃受体诱导角质形成细胞衍生的抗菌肽。通过芳烃受体依赖性转录调节恢复 AD 皮肤中的抗菌肽水平可能是有益的，因为它可以创造一种不易感染和炎症的（抗）微生物环境。这突显了煤焦油在治疗性芳烃受体武器库中的重要性，并强调了芳烃受体作为药物开发的靶点。
