Monasterium Laboratory Skin and Hair Research Solutions GmbH, Münster, Germany.
Zoological Institute, Christian-Albrechts University Kiel, Kiel, Germany.
Skin Pharmacol Physiol. 2023;36(3):117-124. doi: 10.1159/000528402. Epub 2023 Jan 26.
Several olfactory receptors (ORs) are expressed in human skin, where they regulate skin pigmentation, barrier function, wound healing, and hair growth. Previously, we found that the selective activation of OR family 2 subfamily AT member 4 (OR2AT4) by the synthetic, sandalwood-like odorant Sandalore® differentially stimulates the expression of antimicrobial peptides (AMPs) in human scalp hair follicle epithelium ex vivo. As OR2AT4 is also expressed by epidermal keratinocytes, we hypothesized that it may modulate intraepidermal AMP synthesis, thereby contributing to skin microbiome management.
We investigated this hypothesis in organ-cultured human skin in the presence of Sandalore® and antibiotics and evaluated epidermal production of two AMPs, LL37 (cathelicidin) and dermcidin (DCD), as well as OR2AT4, by quantitative immunohistomorphometry. Moreover, we quantified DCD secretion into the culture medium by ELISA and studied the effect of culture medium on selected bacterial and fungal strains.
Topical application of Sandalore®to organ-cultured human skin increased OR2AT4 protein expression, the number of DCD-positive intraepidermal cells, and DCD secretion into culture media, without significantly affecting epidermal LL37 expression. In line with the significantly increased secretion of DCD into the culture medium, we demonstrated, in a spectrophotometric assay, that application of conditioned media from Sandalore®-treated skin promotes Staphylococcus epidermidis, Malassezia restricta, and, minimally, Cutibacterium acnes and inhibits Staphylococcus aureus growth.
In addition to demonstrating for the first time that DCD can be expressed by epidermal keratinocytes, our pilot study suggests that topical treatment of human skin with a cosmetic odorant (Sandalore®) has the potential to alter the composition of the human skin microbiome through the selective upregulation of DCD. If confirmed, Sandalore® could become an attractive adjuvant, nondrug treatment for dermatoses characterized by dysbiosis due to overgrowth of S. aureus and Malassezia, such as atopic dermatitis and seborrheic dermatitis.
几种嗅觉受体（ORs）在人类皮肤中表达，它们调节皮肤色素沉着、屏障功能、伤口愈合和毛发生长。此前，我们发现，人工合成的檀香气味剂桑德罗（Sandalore®）选择性激活 OR 家族 2 亚家族 AT 成员 4（OR2AT4），可在体外差异刺激人头皮毛囊上皮的抗菌肽（AMPs）的表达。由于 OR2AT4 也由表皮角质形成细胞表达，我们假设它可能调节表皮内 AMP 的合成，从而有助于皮肤微生物组的管理。
我们在存在桑德罗（Sandalore®）和抗生素的情况下，在器官培养的人类皮肤中研究了这一假设，并通过定量免疫组织形态计量法评估了表皮产生的两种 AMPs（LL37（抗菌肽）和 dermcidin（DCD））以及 OR2AT4 的情况。此外，我们通过 ELISA 定量测定 DCD 分泌到培养基中的量，并研究了培养基对选定细菌和真菌菌株的影响。
桑德罗（Sandalore®）外用至器官培养的人类皮肤增加了 OR2AT4 蛋白表达、DCD 阳性表皮细胞数量和 DCD 分泌到培养基中，但对表皮 LL37 表达没有显著影响。与 DCD 分泌到培养基中的显著增加一致，我们在分光光度测定中证明，来自桑德罗（Sandalore®）处理皮肤的条件培养基促进表皮葡萄球菌、限制性马拉色菌生长，最小程度上抑制金黄色葡萄球菌生长。
除了首次证明表皮角质形成细胞可以表达 DCD 外，我们的初步研究表明，局部应用化妆品气味剂（桑德罗（Sandalore®））有可能通过选择性上调 DCD 来改变人类皮肤微生物组的组成。如果得到证实，桑德罗（Sandalore®）可能成为一种有吸引力的辅助、非药物治疗方法，用于治疗因金黄色葡萄球菌和马拉色菌过度生长而导致微生态失调的皮肤病，如特应性皮炎和脂溢性皮炎。
