January 20, 2018

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

Key Points
Question  Is the skin microbiome in patients with atopic dermatitis (AD) associated with disease severity and filaggrin gene mutations?
Findings  In this case-control study, bacterial diversity (alpha diversity) of the skin microbiome in patients with AD was inversely correlated with disease severity for both lesional and nonlesional skin. Skin microbiome composition (beta diversity) in nonlesional skin of patients with AD was linked to the presence of filaggrin gene mutations.
Meaning  The findings of this study suggest that the severity of AD influences the skin microbiome globally, even in nonlesional skin. Furthermore, our findings propose a possible association between skin microbiome and host genetics.

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.

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