Dysbiosis of the skin microbiota is increasingly implicated as a contributor to the pathogenesis of atopic dermatitis (AD). We previously reported first-in-human safety and clinical activity results from topical application of the commensal skin bacterium Roseomonas mucosa for the treatment of AD in 10 adults and 5 children older than 9 years of age. Here, we examined the potential mechanism of action of R. mucosa treatment and its impact on children with AD less than 7 years of age, the most common age group for children with AD. In 15 children with AD, R. mucosa treatment was associated with amelioration of disease severity, improvement in epithelial barrier function, reduced Staphylococcus aureus burden on the skin, and a reduction in topical steroid requirements without severe adverse events. Our observed response rates to R. mucosa treatment were greater than those seen in historical placebo control groups in prior AD studies. Skin improvements and colonization by R. mucosa persisted for up to 8 months after cessation of treatment. Analyses of cellular scratch assays and the MC903 mouse model of AD suggested that production of sphingolipids by R. mucosa, cholinergic signaling, and flagellin expression may have contributed to therapeutic impact through induction of a TNFR2-mediated epithelial-to-mesenchymal transition. These results suggest that a randomized, placebo-controlled trial of R. mucosa treatment in individuals with AD is warranted and implicate commensals in the maintenance of the skin epithelial barrier.

皮肤微生物群的失调越来越多地被认为是特应性皮炎 (AD) 发病机制的一个因素。我们之前报道了局部应用共生皮肤细菌玫瑰单胞菌治疗 10 名成人和 5 名 9 岁以上儿童的 AD 的首次人体安全性和临床活性结果。在这里，我们研究了R. 粘膜治疗的潜在作用机制及其对 7 岁以下 AD 儿童（AD 儿童最常见的年龄组）的影响。在 15 名 AD 儿童中，R. 粘膜治疗与疾病严重程度的改善、上皮屏障功能的改善、金黄色葡萄球菌的减少有关皮肤负担，减少局部类固醇的需求，而没有严重的不良事件。我们观察到的对R. 粘膜治疗的反应率高于以往 AD 研究中历史安慰剂对照组的反应率。停止治疗后皮肤改善和黏膜定植持续长达 8 个月。细胞划痕分析和 AD 的 MC903 小鼠模型的分析表明，通过诱导 TNFR2 介导的上皮-间质转化，R. 粘膜产生鞘脂、胆碱能信号传导和鞭毛蛋白表达可能有助于治疗影响。这些结果表明，一项针对R. 粘膜的随机、安慰剂对照试验 对 AD 患者进行治疗是有必要的，并且涉及维持皮肤上皮屏障的共生。