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Skin Microbiome and Filaggrin Gene Mutations in Adult Atopic Dermatitis
abstract
This abstract is available on the publisher's site.
Access this abstract nowImportance
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.
Additional Info
Disclosure statements are available on the authors' profiles:
Association of Disease Severity With Skin Microbiome and Filaggrin Gene Mutations in Adult Atopic Dermatitis
JAMA Dermatol 2018 Jan 17;[EPub Ahead of Print], ML Clausen, T Agner, B Lilje, SM Edslev, TB Johannesen, PS AndersenFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Atopic dermatitis (AD) is a disease of cycles: itch - scratch - itch, and the closely related inflammation—barrier damage–inflammation, for example. In the past several years, we have learned about many other cycles as well, including the idea that Staphylococcus aureus grows more commonly on the skin of AD patients and that, among other mechanisms, it can produce a toxin which further damages the skin barrier to result in—you guessed it—more colonization! S. aureus colonization is directly correlated with decreased skin microbiome diversity, which is correlated with worsening AD. Another cycle, to be sure.
As with any cycle, it can be difficult to know where to start. However, genotype is a pretty good place to begin. Clausen et al tell a compelling story about this cycle that begins with a filaggrin gene (FLG) mutation. FLG mutations are strongly correlated with AD, and are also shown here to be correlated with decreased skin bacterial diversity in AD patients. If this bears out in larger studies, it could settle the “chicken or the egg” argument once and for all, at least for some patients. A genetic deficiency in filaggrin production could pave the way for abnormal skin microbiota, opening the door to S. aureus colonization, and setting into motion the vicious cycle of AD. Perhaps most importantly, with better understanding of these cycles and how they may begin, therapeutic targets emerge at every step, highlighting possibilities for providing relief and pushing toward virtuous cycles of skin barrier, microbiota, and overall health.