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

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.

SUBMITTER: Myles IA

PROVIDER: S-EPMC6012572 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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

Myles Ian A IA Earland Noah J NJ Anderson Erik D ED Moore Ian N IN Kieh Mark D MD Williams Kelli W KW Saleem Arhum A Fontecilla Natalia M NM Welch Pamela A PA Darnell Dirk A DA Barnhart Lisa A LA Sun Ashleigh A AA Uzel Gulbu G Datta Sandip K SK

JCI insight 20180503 9

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 w ...[more]

PMID: 29720571

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Project description:BACKGROUND:Skin barrier dysfunction plays a key role in atopic dermatitis (AD). This impairment is related to altered composition and metabolism of epidermal sphingolipids and a deficiency of ceramides. Glycosaminoglycans (GAGs), and especially hyaluronic acid, could be useful in the management of AD. This study aimed to evaluate the effects of a novel topical treatment consisting of sphingolipids and GAGs extracts in dogs with AD. This formulation is different from previously tested products because the sphingolipid extract contained high amounts of sphingomyelin, a precursor of ceramides, and this has been shown to enhance endogenous synthesis of ceramides and to increase lamellar-related structures in vitro. Thus, it was hypothesized that this formulation could improve clinical disease and skin barrier function in patients with AD. RESULTS:Twelve house dust mite (HDM) allergic atopic beagle dogs were randomized into two groups: control (n = 6; no treatment) or treatment (n = 6; topical sphingolipids and GAGs twice weekly for 8 weeks). Dogs were challenged with allergen twice weekly and the severity of dermatitis was scored using the canine atopic dermatitis and extent severity index (CADESI-03) once weekly. Skin barrier function (measurement of transepidermal water loss) and severity of pruritus (both pruritus visual analog scale [PVAS] and pruritus timed episodes) were assessed at 0, 4 and 8 weeks of treatment. Assessments were done by personnel unaware of group allocation. Complete blood count, serum biochemistry and stratum corneum (SC) lipidomics analyses were done at baseline and at week 8. Compared to baseline, significant increases in CADESI (P = 0.0003) and PVAS (P = 0.041) were observed only in the control group, and SC polyunsaturated fatty acids increased significantly only with treatment (P = 0.039). Compared to control, treatment group had a significantly lower CADESI after 1 week (P = 0.0078) and a significantly lower PVAS after 8 weeks (P = 0.0448). Treatment was well tolerated. CONCLUSIONS:In this study in dogs with AD, a new topical formulation containing sphingomyelin-rich sphingolipids plus GAGs extracts attenuated the clinical worsening induced by HDM, supporting its use in atopic patients, either as an adjunctive treatment or used as monotherapy in certain cases.

Dataset Information

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

Publications

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

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