Changes in Skin and Nasal Microbiome and Staphylococcal Species Following Treatment of Atopic Dermatitis with Dupilumab.

Maja-Lisa Clausen,Paal Skytt Andersen,Caroline Meyer Olesen,Tove Agner,Emma Guttman-Yassky,Anna Cäcilia Ingham,Simon Francis Thomsen,Yasemin Topal Yüksel,Sofie Marie Edslev

doi:10.3390/microorganisms9071487

Abstract

Investigation of changes in the skin microbiome following treatment of atopic dermatitis (AD) with dupilumab may provide valuable insights into the skin microbiome as a therapeutic target. The aim of this study is to assess changes in the AD skin microbiome following treatment of AD with dupilumab (n = 27). E-swabs were collected from nose, lesional, and nonlesional skin before and after 16 weeks of dupilumab therapy, and the microbiome was analyzed by 16S rRNA and tuf gene sequencing. Data for 17 patients with milder disease receiving treatment with non-targeted therapies are also presented. The results show that both groups experienced clinical improvement (p < 0.001) following dupilumab therapy and that Shannon diversity increased and bacterial community structure changed. The relative abundance of the genus Staphylococcus (S.) and S. aureus decreased, while that of S. epidermidis and S. hominis increased. No significant changes were observed for patients receiving non-targeted treatments. The increases in S. epidermidis and S. hominis and the decrease in S. aureus correlated with clinical improvement. Furthermore, changes in S. hominis and S. epidermidis correlated inversely with S. aureus. In conclusion, treatment with dupilumab significantly changed the skin microbiome and decreased S. aureus. Our results suggest a favorable role of commensal staphylococci in AD.

Highlights

The pathogenesis of atopic dermatitis (AD) is characterized by the interplay between activation of the Th2/Th22-skewed immune response and epidermal barrier impairment [1,2]. This is paralleled by changes in the skin microbiome, with decreased bacterial diversity and increased colonization with Staphylococcus aureus (S. aureus), which correlates with disease severity [3,4,5,6]
Our study showed that dupilumab therapy was related to significant changes in the skin microbiome, with increased Shannon diversity and changes in bacterial community structure
Ongoing research is working with manipulating the skin microbiome in the therapeutic management of AD [40,41], and initial pilot trials showed that topical application of coagulase negative staphylococci (CoNS) [40] and Roseomonas mucosa [42] decreased disease severity

Summary

Introduction

The pathogenesis of atopic dermatitis (AD) is characterized by the interplay between activation of the Th2/Th22-skewed immune response and epidermal barrier impairment [1,2]. This is paralleled by changes in the skin microbiome, with decreased bacterial diversity and increased colonization with Staphylococcus aureus (S. aureus), which correlates with disease severity [3,4,5,6]. S. aureus expresses a broad spectrum of virulence factors that aggravate the disease [9,10,11] Commensal staphylococcal species, such as S. epidermidis and S. hominis, work in concert with host immunity to limit pathogen colonization [12,13,14,15], and were recently shown to be reduced in AD [16]. Deficiency of commensal staphylococci may be related to the increased S. aureus colonization and disease severity in AD.

Objectives

Methods

Results

Conclusion