Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin, and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics, and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analyzed the largest cohort and set of distinct, clinically relevant body habitats to date. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families, and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology, and translational applications of the human microbiome.

The skin is the human body’s largest organ, colonized by a diverse milieu of microorganisms, most of which are harmless or even beneficial to their host. Colonization is driven by the ecology of the skin surface, which is highly variable depending on topographical location, endogenous host factors and exogenous environmental factors. The cutaneous innate and adaptive immune responses can modulate the skin microbiota, but the microbiota also functions in educating the immune system. The development of molecular methods to identify microorganisms has led to an emerging view of the resident skin bacteria as highly diverse and variable. An enhanced understanding of the skin microbiome is necessary to gain insight into microbial involvement in human skin disorders and to enable novel promicrobial and antimicrobial therapeutic approaches for their treatment.

Human skin is a large, heterogeneous organ that protects the body from pathogens while sustaining microorganisms that influence human health and disease. Our analysis of 16S ribosomal RNA gene sequences obtained from 20 distinct skin sites of healthy humans revealed that physiologically comparable sites harbor similar bacterial communities. The complexity and stability of the microbial community are dependent on the specific characteristics of the skin site. This topographical and temporal survey provides a baseline for studies that examine the role of bacterial communities in disease states and the microbial interdependencies required to maintain healthy skin.The skin is a critical interface between the human body and its external environment, preventing loss of moisture and barring entry of pathogenic organisms (1). The skin is also an ecosystem, harboring microbial communities that live in a range of physiologically and topographically distinct niches (2). For example, hairy, moist underarms lie a short distance from smooth dry forearms, but these two niches are likely as ecologically dissimilar as rainforests are to deserts. Traditional culture-based characterizations of the skin microbiota are biased toward species that readily grow under standard laboratory conditions, such as Staphylococci spp. However, †To whom correspondence should be addressed. jsegre@nhgri.nih.gov. * See supporting online material for names of group members. Characterizing the microbiota that inhabit specific sites may provide insight into the delicate balance between skin health and disease. Certain dermatological disorders manifest at stereotypical skin sites [e.g., psoriasis on the outer elbow and atopic dermatitis (eczema) on the inner bend of the elbow]. Moreover, antibiotic exposure, modified hygienic practices, and lifestyle changes have the potential to alter the skin microbiome selectively and may underlie the increased incidence of human disorders such as atopic dermatitis. Understanding naturally occurring symbiotic microbial communities will provide insight into the conditions that favor the emergence of antibiotic-resistant organisms [e.g., the highly pathogenic strain of methicillin-resistant S. aureus, which acquired genes that promote growth on skin from the symbiont S. epidermidis (6)].We characterized the topographical and temporal diversity of the human skin microbiome with the use of 16S rRNA gene phylotyping, and generated 112,283 near-full-length bacterial 16S gene sequences from samples of 20 diverse skin sites on each of 10 healthy humans (7) (fig. S1 and table S1). Nineteen bacterial phyla were detected, but most sequences were assigned to four phyla: Actinobacteria (51.8%), Firmicutes (24.4%), Proteobacteria (16.5%), and Bacteroidetes (6.3%). Of the 205 identified genera represented by at least five sequences, three were associated with more than 62% of the sequences: Corynebacteria (22.8%; Actinobacteria), Propionibacteria (23.0%; Actinobacteria), and Staphylococci (16.8%; Firmicutes). At the species...

Functioning as the exterior interface of the human body with the environment, skin acts as a physical barrier to prevent the invasion of foreign pathogens while providing a home to the commensal microbiota. The harsh physical landscape of skin, particularly the desiccated, nutrient-poor, acidic environment, also contributes to the adversity that pathogens face when colonizing human skin. Despite this, the skin is colonized by a diverse microbiota. In this Review, we describe amplicon and shotgun metagenomic DNA sequencing studies that have been used to assess the taxonomic diversity of microorganisms that are associated with skin from the kingdom to the strain level. We discuss recent insights into skin microbial communities, including their composition in health and disease, the dynamics between species and interactions with the immune system, with a focus on Propionibacterium acnes, Staphylococcus epidermidis and Staphylococcus aureus.

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.

A variety of microbial communities and their genes (microbiome) exist throughout the human body, playing fundamental roles in human health and disease. The NIH funded Human Microbiome Project (HMP) Consortium has established a population-scale framework which catalyzed significant development of metagenomic protocols resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 to 18 body sites up to three times, which to date, have generated 5,177 microbial taxonomic profiles from 16S rRNA genes and over 3.5 Tb of metagenomic sequence. In parallel, approximately 800 human-associated reference genomes have been sequenced. Collectively, these data represent the largest resource to date describing the abundance and variety of the human microbiome, while providing a platform for current and future studies.

SummaryThe varied topography of human skin offers a unique opportunity to study how the body’s microenvironments influence the functional and taxonomic composition of microbial communities. Phylogenetic marker gene-based studies have identified many bacteria and fungi that colonize distinct skin niches. Here, metagenomic analyses of diverse body sites in healthy humans demonstrate that local biogeography and strong individuality define the skin microbiome. We developed a relational analysis of bacterial, fungal, and viral communities, which showed not only site-specificity but also individual signatures. We further identified strain-level variation of dominant species as heterogeneous and multiphyletic. Reference-free analyses captured the uncharacterized metagenome through the development of a multi-kingdom gene catalog, which was used to uncover genetic signatures of species lacking reference genomes. This work is foundational for human disease studies investigating inter-kingdom interactions, metabolic changes, and strain tracking and defines the dual influence of biogeography and individuality on microbial composition and function.

Traditional culture-based methods have incompletely defined the etiology of common recalcitrant human fungal skin diseases including athlete’s foot and toenail infections. Skin protects humans from invasion by pathogenic microorganisms, while providing a home for diverse commensal microbiota1. Bacterial genomic sequence data have generated novel hypotheses about species and community structures underlying human disorders2,3,4. However, microbial diversity is not limited to bacteria; microorganisms such as fungi also play major roles in microbial community stability, human health and disease5. Genomic methodologies to identify fungal species and communities have been limited compared with tools available for bacteria6. Fungal evolution can be reconstructed with phylogenetic markers, including ribosomal RNA gene regions and other highly conserved genes7. Here, we sequenced and analyzed fungal communities of 14 skin sites in 10 healthy adults. Eleven core body and arm sites were dominated by Malassezia fungi, with species-level classifications revealing greater topographical resolution between sites. By contrast, three foot sites, plantar heel, toenail, and toeweb, exhibited tremendous fungal diversity. Concurrent analysis of bacterial and fungal communities demonstrated that skin physiologic attributes and topography differentially shape these two microbial communities. These results provide a framework for future investigation of interactions between pathogenic and commensal fungal and bacterial communities in maintaining human health and contributing to disease pathogenesis.