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First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis
Ian A. Myles, … , Gulbu Uzel, Sandip K. Datta
Ian A. Myles, … , Gulbu Uzel, Sandip K. Datta
Published May 3, 2018
Citation Information: JCI Insight. 2018;3(9):e120608. https://doi.org/10.1172/jci.insight.120608.
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Research Article Dermatology Immunology

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

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Abstract

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.

Authors

Ian A. Myles, Noah J. Earland, Erik D. Anderson, Ian N. Moore, Mark D. Kieh, Kelli W. Williams, Arhum Saleem, Natalia M. Fontecilla, Pamela A. Welch, Dirk A. Darnell, Lisa A. Barnhart, Ashleigh A. Sun, Gulbu Uzel, Sandip K. Datta

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Figure 3

Topical Roseomonas mucosa shows activity against atopic dermatitis in children.

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Topical Roseomonas mucosa shows activity against atopic dermatitis in ch...
Mean (scarlet) and individual (gray; n = 5) SCORAD values (A) and percentage improvement (B) during treatment. Dotted line (B) indicates improvement level that is inconsistent with null hypothesis (see Methods). (C) Mean and individual pruritus. (D) Mean and individual patient-reported days of topical steroid use per month for the 3 months prior to enrollment (week 0) and during treatment. (E) Pretreatment photos from enrollment (week 0), after treatment (week 16) for the popliteal fossae for patient S5 (see Supplemental Table 1). (F) Ratio of Staphylococcus aureus to coagulase-negative staphylococci from the antecubital (AC) fossa as determined by culture. Significance determined by 2-tailed Student’s t test and nonparametric Wilcoxon’s matched-pairs test. *P < 0.05, **P < 0.01 as determined versus enrollment value.

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