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First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis
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
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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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 2

Topical Roseomonas mucosa shows activity against atopic dermatitis in adults.

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Topical Roseomonas mucosa shows activity against atopic dermatitis in ad...
Mean (bars) and individual (circles; n = 10) before- and after-treatment scores for objective intensity (A) and subjective pruritus (B) as measured by SCORAD. (C) Antecubital-specific SCORAD; sum of local intensity and pruritus scores. (D) Mean (scarlet) and individual (gray) self-reported steroid use (days/month) from the 6 weeks prior to enrollment (week 0), after treatment (week 6), and after washout (week 10). Patients were instructed to maintain their home regimens throughout active treatment; however, patients 2 and 9 discontinued topical steroids upon initiation of R. mucosa treatment. (E) Pretreatment photos from enrollment, after treatment, and after washout (photo taken by patient) for the dominant-arm antecubital fossa and the face for patient 7 (see Supplemental Table 2). (F) Summary of areas of involvement (scarlet shading), asymptomatic areas (gray), and areas directly treated (check mark). Significance determined by 2-tailed Student’s t test and nonparametric Wilcoxon’s matched-pairs test. *P < 0.05, **P < 0.01.

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