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Longitudinal Evaluation of the Skin Microbiome and Association with Microenvironment and Treatment in Canine Atopic Dermatitis.

ABSTRACT: Host-microbe interactions may play a fundamental role in the pathogenesis of atopic dermatitis, a chronic relapsing inflammatory skin disorder characterized by universal colonization with Staphylococcus species. To examine the relationship between epidermal barrier function and the cutaneous microbiota in atopic dermatitis, this study used a spontaneous model of canine atopic dermatitis. In a cohort of 14 dogs with canine atopic dermatitis, the skin microbiota were longitudinally evaluated with parallel assessment of skin barrier function at disease flare, during antimicrobial therapy, and post-therapy. Sequencing of the bacterial 16S ribosomal RNA gene showed decreased bacterial diversity and increased proportions of Staphylococcus (S. pseudintermedius in particular) and Corynebacterium species compared with a cohort of healthy control dogs (n = 16). Treatment restored bacterial diversity with decreased proportions of Staphylococcus species, concurrent with decreased canine atopic dermatitis severity. Skin barrier function, as measured by corneometry, pH, and transepidermal water loss also normalized with treatment. Bacterial diversity correlated with transepidermal water loss and pH level but not with corneometry results. These findings provide insights into the relationship between the cutaneous microbiome and skin barrier function in atopic dermatitis, show the impact of antimicrobial therapy on the skin microbiome, and highlight the utility of canine atopic dermatitis as a spontaneous nonrodent model of atopic dermatitis.

SUBMITTER: Bradley CW

PROVIDER: S-EPMC4877200 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Longitudinal Evaluation of the Skin Microbiome and Association with Microenvironment and Treatment in Canine Atopic Dermatitis.

Bradley Charles W CW Morris Daniel O DO Rankin Shelley C SC Cain Christine L CL Misic Ana M AM Houser Timothy T Mauldin Elizabeth A EA Grice Elizabeth A EA

The Journal of investigative dermatology 20160206 6

Host-microbe interactions may play a fundamental role in the pathogenesis of atopic dermatitis, a chronic relapsing inflammatory skin disorder characterized by universal colonization with Staphylococcus species. To examine the relationship between epidermal barrier function and the cutaneous microbiota in atopic dermatitis, this study used a spontaneous model of canine atopic dermatitis. In a cohort of 14 dogs with canine atopic dermatitis, the skin microbiota were longitudinally evaluated with ...[more]

PMID: 26854488

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Project description:ImportanceSkin microbiome correlates with disease severity for lesional and nonlesional skin, indicating a global influence of atopic dermatitis (AD). A relation between skin microbiome and filaggrin gene (FLG) mutations proposes a possible association between skin microbiome and host genetics.ObjectivesTo assess skin and nasal microbiome diversity and composition in patients with AD and compare with healthy controls, and to investigate the microbiome in relation to disease severity and FLG mutations in patients with AD.Design, setting, and participantsAn observational case-control study of 45 adult healthy controls and 56 adult patients with AD was carried out from January 2015 to June 2015 in a tertiary referral center, Department of Dermatology, Bispebjerg Hospital, Denmark.ExposuresBacterial swabs were taken from patients with AD (lesional skin, nonlesional skin, and anterior nares) and from healthy controls (nonlesional skin and anterior nares). Eczema severity was assessed and FLG mutations noted. Bacterial DNA was extracted from swabs, and V3-V4 16S rDNA regions amplified with PCR. Samples were analyzed at Statens Serum Institut September 2015 to September 2016. Bioinformatics analyses of the microbiome were analyzed using R statistical software (version 3.3.1, R Foundation Inc).Main outcomes and measuresSkin microbiomes were investigated using next-generation sequencing targeting 16S ribosomal RNA.ResultsMicrobiome alpha diversity was lower in patients with AD compared with healthy controls in nonlesional skin (effect size, 0.710; 95% CI, 0.27-1.15; P = .002), lesional skin (effect size, 0.728; 95% CI, 0.35-1.33; P = .001), and nose (effect size, 1.111; 95% CI, 0.48-0.94; P < .001). Alpha diversity was inversely correlated with disease severity for lesional (effect size, 0.530; 95% CI, 0.23-1.64; P = .02) and nonlesional skin (effect size, 0.451; 95% CI, 0.04-2.44; P = .04) in patients with AD. Microbiome composition in AD nonlesional skin was linked to FLG mutations.Conclusions and relevanceAn altered microbiome composition in patients with AD in nonlesional skin, lesional skin, as well as nose, suggests a global influence of AD. Microbiome composition in AD nonlesional skin is associated with FLG mutations, proposing a possible association between the skin microbiome and host genetics.

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

Longitudinal Evaluation of the Skin Microbiome and Association with Microenvironment and Treatment in Canine Atopic Dermatitis.

Publications

Longitudinal Evaluation of the Skin Microbiome and Association with Microenvironment and Treatment in Canine Atopic Dermatitis.

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