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      Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis

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          Abstract

          Atopic dermatitis (AD) has long been associated with Staphylococcus aureus skin colonization or infection and is typically managed with regimens that include antimicrobial therapies. However, the role of microbial communities in the pathogenesis of AD is incompletely characterized. To assess the relationship between skin microbiota and disease progression, 16S ribosomal RNA bacterial gene sequencing was performed on DNA obtained directly from serial skin sampling of children with AD. The composition of bacterial communities was analyzed during AD disease states to identify characteristics associated with AD flares and improvement post-treatment. We found that microbial community structures at sites of disease predilection were dramatically different in AD patients compared with controls. Microbial diversity during AD flares was dependent on the presence or absence of recent AD treatments, with even intermittent treatment linked to greater bacterial diversity than no recent treatment. Treatment-associated changes in skin bacterial diversity suggest that AD treatments diversify skin bacteria preceding improvements in disease activity. In AD, the proportion of Staphylococcus sequences, particularly S. aureus, was greater during disease flares than at baseline or post-treatment, and correlated with worsened disease severity. Representation of the skin commensal S. epidermidis also significantly increased during flares. Increases in Streptococcus, Propionibacterium, and Corynebacterium species were observed following therapy. These findings reveal linkages between microbial communities and inflammatory diseases such as AD, and demonstrate that as compared with culture-based studies, higher resolution examination of microbiota associated with human disease provides novel insights into global shifts of bacteria relevant to disease progression and treatment.

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          Most cited references55

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          Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities.

          mothur aims to be a comprehensive software package that allows users to use a single piece of software to analyze community sequence data. It builds upon previous tools to provide a flexible and powerful software package for analyzing sequencing data. As a case study, we used mothur to trim, screen, and align sequences; calculate distances; assign sequences to operational taxonomic units; and describe the alpha and beta diversity of eight marine samples previously characterized by pyrosequencing of 16S rRNA gene fragments. This analysis of more than 222,000 sequences was completed in less than 2 h with a laptop computer.
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            Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis.

            Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.
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              NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007.

              To describe the frequency of selected antimicrobial resistance patterns among pathogens causing device-associated and procedure-associated healthcare-associated infections (HAIs) reported by hospitals in the National Healthcare Safety Network (NHSN). Data are included on HAIs (ie, central line-associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonia, and surgical site infections) reported to the Patient Safety Component of the NHSN between January 2006 and October 2007. The results of antimicrobial susceptibility testing of up to 3 pathogenic isolates per HAI by a hospital were evaluated to define antimicrobial-resistance in the pathogenic isolates. The pooled mean proportions of pathogenic isolates interpreted as resistant to selected antimicrobial agents were calculated by type of HAI and overall. The incidence rates of specific device-associated infections were calculated for selected antimicrobial-resistant pathogens according to type of patient care area; the variability in the reported rates is described. Overall, 463 hospitals reported 1 or more HAIs: 412 (89%) were general acute care hospitals, and 309 (67%) had 200-1,000 beds. There were 28,502 HAIs reported among 25,384 patients. The 10 most common pathogens (accounting for 84% of any HAIs) were coagulase-negative staphylococci (15%), Staphylococcus aureus (15%), Enterococcus species (12%), Candida species (11%), Escherichia coli (10%), Pseudomonas aeruginosa (8%), Klebsiella pneumoniae (6%), Enterobacter species (5%), Acinetobacter baumannii (3%), and Klebsiella oxytoca (2%). The pooled mean proportion of pathogenic isolates resistant to antimicrobial agents varied significantly across types of HAI for some pathogen-antimicrobial combinations. As many as 16% of all HAIs were associated with the following multidrug-resistant pathogens: methicillin-resistant S. aureus (8% of HAIs), vancomycin-resistant Enterococcus faecium (4%), carbapenem-resistant P. aeruginosa (2%), extended-spectrum cephalosporin-resistant K. pneumoniae (1%), extended-spectrum cephalosporin-resistant E. coli (0.5%), and carbapenem-resistant A. baumannii, K. pneumoniae, K. oxytoca, and E. coli (0.5%). Nationwide, the majority of units reported no HAIs due to these antimicrobial-resistant pathogens.
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                Author and article information

                Journal
                Genome Res
                Genome Res
                GENOME
                Genome Research
                Cold Spring Harbor Laboratory Press
                1088-9051
                1549-5469
                May 2012
                : 22
                : 5
                : 850-859
                Affiliations
                [1 ]Dermatology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA;
                [2 ]Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA;
                [3 ]Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA;
                [4 ]Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA;
                [5 ]NIH Intramural Sequencing Center, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA;
                [6 ]Microbiology Service, Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, Maryland 20892, USA
                Author notes
                [7]

                A complete list of of the NISC Comparative Sequencing Program investigators appears at the end of this manuscript.

                [8 ]Corresponding authors. E-mail konghe@ 123456mail.nih.gov . E-mail jsegre@ 123456mail.nih.gov .
                Article
                9518021
                10.1101/gr.131029.111
                3337431
                22310478
                38cf8704-5c42-4a85-8859-c9567526b082
                © 2012, Published by Cold Spring Harbor Laboratory Press

                This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.

                History
                : 23 August 2011
                : 30 January 2012
                Categories
                Research

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