First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis

被引:223
作者
Myles, Ian A. [1 ]
Earland, Noah J. [1 ]
Anderson, Erik D. [1 ]
Moore, Ian N. [2 ]
Kieh, Mark D. [1 ]
Williams, Kelli W. [1 ]
Saleem, Arhum [1 ]
Fontecilla, Natalia M. [1 ]
Welch, Pamela A. [1 ]
Darnell, Dirk A. [1 ]
Barnhart, Lisa A. [1 ]
Sun, Ashleigh A. [1 ]
Uzel, Gulbu [1 ]
Datta, Sandip K. [1 ]
机构
[1] NIAID, Lab Clin Immunol & Microbiol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[2] NIAID, Infect Dis & Pathogenesis Sect, Comparat Med Branch, NIH, Rockville, MD USA
关键词
QUALITY-OF-LIFE; DOUBLE-BLIND; NATURAL-HISTORY; TASK-FORCE; CHILDREN; PLACEBO; GUIDELINES; MANAGEMENT; ECZEMA; COLONIZATION;
D O I
10.1172/jci.insight.120608
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The underlying pathology of atopic dermatitis (AD) includes impaired skin barrier function, susceptibility to Staphylococcus aureus skin infection, immune dysregulation, and cutaneous dysbiosis. Our recent investigation into the potential role of Gram-negative skin bacteria in AD revealed that isolates of one particular commensal, Roseomonas mucosa, collected from healthy volunteers (HVs) improved outcomes in mouse and cell culture models of AD. In contrast, isolates of R. mucosa from patients with AD worsened outcomes in these models. These preclinical results suggested that interventions targeting the microbiome could provide therapeutic benefit for patients with AD. As a first test of this hypothesis in humans, 10 adult and 5 pediatric patients were enrolled in an open-label phase I/II safety and activity trial (the Beginning Assessment of Cutaneous Treatment Efficacy for Roseomonas in Atopic Dermatitis trial; BACTERiAD I/II). Treatment with R. mucosa was associated with significant decreases in measures of disease severity, topical steroid requirement, and S. aureus burden. There were no adverse events or treatment complications. We additionally evaluated differentiating bacterial metabolites and topical exposures that may contribute to the skin dysbiosis associated with AD and/or influence future microbiome-based treatments. These early results support continued evaluation of R. mucosa therapy with a placebo-controlled trial.
引用
收藏
页数:13
相关论文
共 51 条
[1]   Characterization of the skin penetration of a hydrocarbon-based weapons maintenance oil [J].
Arfsten, Darryl P. ;
Garrett, Carol M. ;
Jederberg, Warren W. ;
Wilfong, Erin R. ;
McDougal, James N. .
JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE, 2006, 3 (09) :457-464
[2]   Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood:: ISAAC Phases One and Three repeat multicountry cross-sectional surveys [J].
Asher, M. Innes ;
Montefort, Stephen ;
Bjorksten, Bengt ;
Lai, Christopher K. W. ;
Strachan, David P. ;
Weiland, Stephan K. ;
Williams, Hywel .
LANCET, 2006, 368 (9537) :733-743
[3]  
Bantz Selene K, 2014, J Clin Cell Immunol, V5
[4]   Lipid abnormalities in atopic skin are driven by type 2 cytokines [J].
Berdyshev, Evgeny ;
Goleva, Elena ;
Bronova, Irina ;
Dyjack, Nathan ;
Rios, Cydney ;
Jung, John ;
Taylor, Patricia ;
Jeong, Mingeum ;
Hall, Clifton F. ;
Richers, Brittany N. ;
Norquest, Kathryn A. ;
Zheng, Tao ;
Seibold, Max A. ;
Leung, Donald Y. M. .
JCI INSIGHT, 2018, 3 (04)
[5]   Genetic and epigenetic studies of atopic dermatitis [J].
Bin, Lianghua ;
Leung, Donald Y. M. .
ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY, 2016, 12
[6]   Recent insights into atopic dermatitis and implications for management of infectious complications [J].
Boguniewicz, Mark ;
Leung, Donald Y. M. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2010, 125 (01) :4-13
[7]   Novel concepts of prevention and treatment of atopic dermatitis through barrier and immune manipulations with implications for the atopic march [J].
Czarnowicki, Tali ;
Krueger, James G. ;
Guttman-Yassky, Emma .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2017, 139 (06) :1723-1734
[8]   Clinical significance of Roseomonas species isolated from catheter and blood samples:: Analysis of 36 cases in patients with cancer [J].
Dé, I ;
Rolston, KVI ;
Han, XY .
CLINICAL INFECTIOUS DISEASES, 2004, 38 (11) :1579-1584
[9]   First eczema biologic debuts but price could restrict use [J].
Dolgin, Elie .
NATURE BIOTECHNOLOGY, 2017, 35 (05) :391-392
[10]   Current guidelines for the evaluation and management of atopic dermatitis: A comparison of the Joint Task Force Practice Parameter and American Academy of Dermatology guidelines [J].
Eichenfield, Lawrence F. ;
Ahluwalia, Jusleen ;
Waldman, Andrea ;
Borok, Jenna ;
Udkoff, Jeremy ;
Boguniewicz, Mark .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2017, 139 (04) :S49-S57