10.1101/gr.075549.107Access the most recent version at doi: 2008 18: 1043-1050 originally published online May 23, 2008Genome Res. Elizabeth A. Grice, Heidi H. Kong, Gabriel Renaud, et al. A diversity profile of the human skin microbiota MaterialSupplemental http://genome.cshlp.org/content/suppl/2008/05/27/gr.075549.107.DC1.htmlReferences http://genome.cshlp.org/content/18/7/1043.full.html#related-urlsArticle cited in: http://genome.cshlp.org/content/18/7/1043.full.html#ref-list-1This article cites 32 articles, 17 of which can be accessed free at:Open AccessFreely available online through the Genome Research Open Access option.serviceEmail alerting click heretop right corner of the article orReceive free email alerts when new articles cite this article - sign up in the box at the http://genome.cshlp.org/subscriptions go to: Genome ResearchTo subscribe to Copyright © 2008, Cold Spring Harbor Laboratory Press Cold Spring Harbor Laboratory Press on September 2, 2009 - Published by genome.cshlp.orgDownloaded fromA diversity profile of the human skin microbiotaElizabeth A. Grice,1Heidi H. Kong,2Gabriel Renaud,3Alice C. Young,4NISCComparative Sequencing Program,4Gerard G. Bouffard,3,4Robert W. Blakesley,3,4Tyra G. Wolfsberg,3Maria L. Turner,2and Julia A. Segre1,51Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda,Maryland 20892, USA;2Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutesof Health, Bethesda, Maryland 20892, USA;3Genome Technology Branch, National Human Genome Research Institute,National Institutes of Health, Bethesda, Maryland 20892, USA;4NIH Intramural Sequencing Center (NISC),National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USAThe many layers and structures of the skin serve as elaborate hosts to microbes, including a diversity of commensaland pathogenic bacteria that contribute to both human health and disease. To determine the complexity andidentity of the microbes inhabiting the skin, we sequenced bacterial 16S small-subunit ribosomal RNA genes isolatedfrom the inner elbow of five healthy human subjects. This analysis revealed 113 operational taxonomic units (OTUs;“phylotypes”) at the level of 97% similarity that belong to six bacterial divisions. To survey all depths of the skin,we sampled using three methods: swab, scrape, and punch biopsy. Proteobacteria dominated the skin microbiota at alldepths of sampling. Interpersonal variation is approximately equal to intrapersonal variation when consideringbacterial community membership and structure. Finally, we report strong similarities in the complexity and identityof mouse and human skin microbiota. This study of healthy human skin microbiota will serve to direct futureresearch addressing the role of skin microbiota in health and disease, and metagenomic projects addressing thecomplex physiological interactions between the skin and the microbes that inhabit this environment.[Supplemental material is available online at www.genome.org. The sequence data from this study have beensubmitted to GenBank under accession nos. EU534411–EU540623.]The skin barrier is critical for survival, preventing the escape ofmoisture and invasion by infectious or toxic substances (Segre2006). The skin is also an intricate habitat for a diverse popula-tion of microbiota. During the birthing process and subsequentexposure to the post-natal environment, the skin is colonized bya wide array of microbes, many of which are commensal or sym-biotic. Proposed beneficial roles of resident microbiota includeinhibition of pathogenic species and further processing of skinproteins, free fatty acids, and sebum (Roth and James 1988). Theskin is composed of a variety of niches, including regions with abroad range of pH, temperature, moisture, and sebum content.Furthermore, skin structures such as hair follicles, sebaceous, ec-crine, and apocrine glands comprise subhabitats that may be as-sociated with their own unique microbiota (Marples 1965; Kear-ney et al. 1984).Many lines of evidence suggest a role for microorganismseven in noninfectious skin diseases, such as atopic dermatitis(AD; eczema), rosacea, psoriasis, and acne (Holland et al. 1977;Thomsen et al. 1980; Till et al. 2000; Paulino et al. 2006). Resi-dent microbiota may become pathogenic, sometimes in responseto an impaired skin barrier (Roth and James 1988). This observa-tion underscores the value of a comprehensive characterizationof the healthy skin microbiota to understand its role in thepathogenesis of skin disorders and ultimately to facilitate noveltranslational therapies.Until recently, knowledge of the skin microbiota was lim-ited to culture-dependent assays, although it is estimated thatless then 1% of bacterial species can be cultivated (Staley andKonopka 1985). The 16S small subunit ribosomal (rRNA) genesare universal among prokaryotes and contain species-specificvariable regions that are useful for inferring phylogenetic rela-tionships (Hugenholtz and Pace 1996; Pace 1997). Broad-rangePCR primers that anneal to highly conserved regions flanking thevariable regions of the gene allow amplification from the major-ity of known bacteria. A recent 16S rRNA gene survey from Gaoet al. (2007) shed some light on the composition of the superfi-cial skin microbiota; their findings suggest that the bacteriasampled by swabbing the volar forearm are highly diverse. Fur-thermore, their findings suggest a low level of interpersonal con-sensus and an extremely dynamic microbiota that fluctuatesgreatly in a short span of time.The NIH Roadmap for Medical Research recently launchedthe Human Microbiome Project (HMP) with the mission to com-prehensively characterize human microbiota and analyze its rolein human health and disease state (http://nihroadmap.nih.gov/hmp/). Initial HMP efforts include sampling multiples sites ofhealthy volunteers to determine whether humans share core mi-crobial diversity profiles. Obtaining accurate, representativesamples is a major challenge when surveying microbiota. Forlarge-scale skin sampling, the most practical method of collec-tion would undoubtedly be swabbing because it is simple, quick,and noninvasive. However, swabbing may not accurately repre-sent the resident microbiota of full thickness skin. Skin scrapingoffers intermediate benefits by allowing collection of superficialskin cells and associated
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