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成人特应性皮炎的疾病严重程度与皮肤微生物组和丝聚合蛋白基因突变的相关性。

Association of Disease Severity With Skin Microbiome and Filaggrin Gene Mutations in Adult Atopic Dermatitis.

机构信息

Department of Dermatology, Bispebjerg University Hospital, Copenhagen, Denmark.

Statens Serum Institut, Department of Bacteria, Parasites, and Fungi, Statens Serum Institut, Copenhagen, Denmark.

出版信息

JAMA Dermatol. 2018 Mar 1;154(3):293-300. doi: 10.1001/jamadermatol.2017.5440.

Abstract

IMPORTANCE

Skin 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.

OBJECTIVES

To 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 PARTICIPANTS: An 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.

EXPOSURES

Bacterial 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 MEASURES

Skin microbiomes were investigated using next-generation sequencing targeting 16S ribosomal RNA.

RESULTS

Microbiome 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 RELEVANCE

An 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.

摘要

重要性

皮肤微生物组与病变和非病变皮肤的疾病严重程度相关,表明特应性皮炎(AD)具有全球性影响。皮肤微生物组与丝聚合蛋白基因(FLG)突变之间的关系提出了皮肤微生物组与宿主遗传之间可能存在关联。

目的

评估 AD 患者的皮肤和鼻腔微生物组多样性和组成,并与健康对照组进行比较,并研究 AD 患者皮肤微生物组与疾病严重程度和 FLG 突变的关系。

设计、地点和参与者:这是一项 2015 年 1 月至 2015 年 6 月在丹麦比斯加普比耶格医院皮肤科进行的成人 AD 患者和 56 名成人健康对照的观察性病例对照研究。

暴露情况

从 AD 患者(病变皮肤、非病变皮肤和前鼻孔)和健康对照(非病变皮肤和前鼻孔)中采集细菌拭子。评估湿疹严重程度并注意到 FLG 突变。从拭子中提取细菌 DNA,并用 PCR 扩增 V3-V4 16S rDNA 区域。2015 年 9 月至 2016 年 9 月在 Statens Serum Institut 进行微生物组的生物信息学分析。使用 R 统计软件(版本 3.3.1,R 基金会公司)分析微生物组的 alpha 多样性。

主要结果和测量

使用靶向 16S 核糖体 RNA 的下一代测序技术研究皮肤微生物组。

结果

与健康对照组相比,AD 患者的非病变皮肤(效应大小,0.710;95%CI,0.27-1.15;P=0.002)、病变皮肤(效应大小,0.728;95%CI,0.35-1.33;P=0.001)和鼻子(效应大小,1.111;95%CI,0.48-0.94;P<0.001)的皮肤微生物组 alpha 多样性较低。AD 患者病变皮肤(效应大小,0.530;95%CI,0.23-1.64;P=0.02)和非病变皮肤(效应大小,0.451;95%CI,0.04-2.44;P=0.04)的 alpha 多样性与疾病严重程度呈负相关。AD 患者非病变皮肤的微生物组组成与 FLG 突变有关。

结论和相关性

AD 患者非病变皮肤、病变皮肤和鼻子的皮肤微生物组组成发生改变,表明 AD 具有全球性影响。AD 非病变皮肤的微生物组组成与 FLG 突变有关,这表明皮肤微生物组与宿主遗传之间可能存在关联。

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