Myles Ian A, Williams Kelli W, Reckhow Jensen D, Jammeh Momodou L, Pincus Nathan B, Sastalla Inka, Saleem Danial, Stone Kelly D, Datta Sandip K
Bacterial Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Maryland, USA.
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Maryland, USA.
JCI Insight. 2016 Jul 7;1(10). doi: 10.1172/jci.insight.86955.
Atopic dermatitis (AD) is characterized by reduced barrier function, reduced innate immune activation, and susceptibility to . Host susceptibility factors are suggested by monogenic disorders associated with AD-like phenotypes and can be medically modulated. contributes to AD pathogenesis and can be mitigated by antibiotics and bleach baths. Recent work has revealed that the skin microbiome differs significantly between healthy controls and patients with AD, including decreased Gram-negative bacteria in AD. However, little is known about the potential therapeutic benefit of microbiome modulation. To evaluate whether parameters of AD pathogenesis are altered after exposure to different culturable Gram-negative bacteria (CGN) collected from human skin, CGN were collected from healthy controls and patients with AD. Then, effects on cellular and culture-based models of immune, epithelial, and bacterial function were evaluated. Representative strains were evaluated in the MC903 mouse model of AD. We found that CGN taken from healthy volunteers but not from patients with AD were associated with enhanced barrier function, innate immunity activation, and control of . Treatment with CGN from healthy controls improved outcomes in a mouse model of AD. These findings suggest that a live-biotherapeutic approach may hold promise for treatment of patients with AD.
特应性皮炎(AD)的特征是屏障功能降低、先天免疫激活减弱以及易感性增加。与AD样表型相关的单基因疾病提示了宿主易感性因素,且这些因素可通过医学手段进行调节。[此处原文缺失内容]导致AD发病机制的产生,并且可通过抗生素和漂白浴来减轻。最近的研究表明,健康对照者和AD患者的皮肤微生物群存在显著差异,包括AD患者中革兰氏阴性菌减少。然而,关于微生物群调节的潜在治疗益处知之甚少。为了评估暴露于从人皮肤收集的不同可培养革兰氏阴性菌(CGN)后AD发病机制参数是否发生改变,从健康对照者和AD患者中收集了CGN。然后,评估其对免疫、上皮和细菌功能的细胞模型及基于培养的模型的影响。在AD的MC903小鼠模型中评估了代表性菌株。我们发现,从健康志愿者而非AD患者身上获取的CGN与增强的屏障功能、先天免疫激活以及[此处原文缺失内容]的控制有关。用来自健康对照者的CGN进行治疗可改善AD小鼠模型的结局。这些发现表明,一种活菌生物治疗方法可能有望用于治疗AD患者。