• 纳入15位过敏性皮炎(AD)儿童接受玫瑰单胞菌治疗,表现出疾病严重程度的改善、上皮屏障功能的改善、皮肤上金黄色葡萄球菌的减少、局部类固醇的需求减少而没有严重不良反应;
  • 玫瑰单胞菌治疗AD反应率显著高于安慰剂对照组,停止治疗后,皮肤的改善和玫瑰单胞菌的定植持续了8个月;
  • 治疗与皮肤微生物群多样性的改变有关;
  • 治疗机制或与诱导TNFR2介导的上皮间充质转化有关,受玫瑰单胞菌的甘油磷脂产物、胆碱信号通路、鞭毛表达的影响。
皮肤微生物群失调或是过敏性皮炎(AD)发病机制的一个因素。之前的报道证明了局部应用皮肤共生菌玫瑰单胞菌治疗10名成人和5名9岁以上儿童具有安全性和临床效果。Science Translational Medicine最近发表的文章,进一步对玫瑰单胞菌治疗AD的机制进行探讨。玫瑰单胞菌或诱导TNFR2介导的上皮间充质转化以及改变皮肤微生物群的多样性,从而改善AD病症。

Therapeutic responses to Roseomonas mucosa in atopic dermatitis may involve lipid-mediated TNF-related epithelial repair



2020-09-09, Article

Abstract & Authors:展开

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.

First Authors:
Craig A Martens,Sandip K Datta

Correspondence Authors:
Ian A Myles

All Authors:
Ian A Myles,Carlo R Castillo,Kent D Barbian,Kishore Kanakabandi,Kimmo Virtaneva,Emily Fitzmeyer,Monica Paneru,Francisco Otaizo-Carrasquero,Timothy G Myers,Tovah E Markowitz,Ian N Moore,Xue Liu,Marc Ferrer,Yosuke Sakamachi,Stavros Garantziotis,Muthulekha Swamydas,Michail S Lionakis,Erik D Anderson,Noah J Earland,Sundar Ganesan,Ashleigh A Sun,Jenna RE Bergerson,Robert A Silverman,Maureen Petersen,Craig A Martens,Sandip K Datta