TY - JOUR

T1 - Association of Disease Severity With Skin Microbiome and Filaggrin Gene Mutations in Adult Atopic Dermatitis

AU - Clausen, Maja Lisa

AU - Agner, Tove

AU - Lilje, Berit

AU - Edslev, Sofie M.

AU - Johannesen, Thor Bech

AU - Andersen, Paal Skytt

PY - 2018/3

Y1 - 2018/3

N2 - 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 microbiomeswere 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.

AB - 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 microbiomeswere 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.

U2 - 10.1001/jamadermatol.2017.5440

DO - 10.1001/jamadermatol.2017.5440

M3 - Journal article

C2 - 29344612

AN - SCOPUS:85043989031

VL - 154

SP - 293

EP - 300

JO - JAMA Dermatology

JF - JAMA Dermatology

SN - 2168-6068

IS - 3

ER -