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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 1

Overview of study design.

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Overview of study design.
Summary of study design for adult (A) and pedi...
Summary of study design for adult (A) and pediatric (B) cohorts. Upon enrollment patients underwent history and physical (H&P), screening blood work, bacterial antecubital skin swab, and assessment of antecubital-specific (A.C.) and total SCORAD values. Patients self-administered the topical, live bacteria in a predetermined dose escalation from 103–105 colony-forming units (CFU) per site. Treatments were twice per week (as indicated by pink arrows) for all adults and for weeks 0–12 for the pediatric cohort. Pediatric patients administered treatments every other day during weeks 13–16. Treatments consisted only of R. mucosa in 250 μl of 10%–15% sucrose. Remote follow-up for solicitation of unexpected problems and/or adverse events (UP/AE; indicated by cell phone icons) was performed weekly during adult treatment and then 4 weeks after discontinuation of therapy. Washout evaluation for pediatric cohort is ongoing.

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