The human distal gut harbors a vast ensemble of microbes (the microbiota) that provide us with important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides1–6. Studies of a small number of unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes6–8, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is utilized and stored3–5. To address the question of how host genotype, environmental exposures, and host adiposity influence the gut microbiome, we have characterized the fecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person’s gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable ‘core microbiome’ at the gene, rather than at the organismal lineage level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity, and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this core are associated with different physiologic states (obese versus lean).

Our adult bodies harbor ~10 times more microbial than human cells. Their genomes (the microbiome) endow us with physiologic capacities that we have not had to evolve on our own and thus are both a manifestation of who we are genetically and metabolically, and a reflection of our state of well-being. Our distal gut is the highest density natural bacterial ecosystem known, the most comprehensively surveyed to date, and the most highly represented in pure culture. It contains more bacterial cells than all of our other microbial communities combined. To obtain a more comprehensive view of our biology, we propose a human gut microbiome initiative (HGMI) that will deliver deep draft whole genome sequences for 100 species representing the bacterial divisions (superkingdoms) known to comprise our distal gut microbiota: 15 of these genomes will be selected for finishing. A cost-effective strategy involves producing the bulk of the coverage by shotgun reads on a 454 Life Sciences pyrosequencer. Long-range linking information will be provided by paired end reads of fosmid subclones using a conventional ABI 3730xl capillary machine. The bulk of our sequencing will use human-derived strains, representing targeted phylotypes, from existing culture collections. The list will be augmented by in vivo culture of a human fecal microbiota in gnotobiotic mice. The latter approach will be used to obtain vastly simplified consortia, or pure cultures of previously uncultured representatives of important gutassociated bacteria. The deposited curated genome sequences will herald another phase of completion of the 'human' genome sequencing project, provide a key reference for metagenome projects, and serve as a model for future initiatives that seek to characterize our other extra-intestinal microbial communities.

Mammals are metagenomic in that they are composed not only of their own gene complements but also those of all of their associated microbes. To understand the co-evolution of the mammals and their indigenous microbial communities, we conducted a network-based analysis of bacterial 16S rRNA gene sequences from the fecal microbiota of humans and 59 other mammalian species living in two zoos and the wild. The results indicate that host diet and phylogeny both influence bacterial diversity, which increases from carnivory to omnivory to herbivory, that bacterial communities codiversified with their hosts, and that the gut microbiota of humans living a modern lifestyle is typical of omnivorous primates.Our 'metagenome' is a composite of Homo sapiens genes and genes present in the genomes of the trillions of microbes that colonize our adult bodies (1). The vast majority of these microbes live in our distal guts. 'Our' microbial genomes (microbiome) encode metabolic functions that we have not had to evolve wholly on our own, including the ability to extract energy and nutrients from our diet. It is unclear how distinctively human our gut microbiota is, or how modern H. sapiens' ability to construct a wide range of diets has affected our gut microbial ecology. In this study we address two general questions concerning the evolution of mammals: how do diet and host phylogeny shape mammalian microbiota? When a mammalian species acquires a new dietary niche, how does its gut microbiota relate to the microbiota of its close relatives?The acquisition of a new diet is a fundamental driver for the evolution of new species. Coevolution, the reciprocal adaptations occurring between interacting species (2), produces dramatic physiological changes that are often recorded in fossil remains. For instance, although mammals made their first appearance on the world stage in the Jurassic (~160 Ma), most modern species arose during the Quaternary (1.8 Ma to present (5)), when C4-grasslands expanded in response to a fall in atmospheric CO 2 levels and/or climate changes (6-8). The switch to a C4 plant-dominated diet selected for herbivores with high-crowned teeth (3) and longer gut retention times necessary for the digestion of lower-quality forage (9). However, these adaptations may not suffice for the exploitation of a new dietary niche. The community

Elucidating the biogeography of bacterial communities on the human body is critical for establishing healthy baselines from which to detect differences associated with diseases. To obtain an integrated view of the spatial and temporal distribution of the human microbiota, we surveyed bacteria from up to 27 sites in 7–9 healthy adults on four occasions. We found that community composition was determined primarily by body habitat. Within habitats, interpersonal variability was high, while individuals exhibited minimal temporal variability. Several skin locations harbored more diverse communities than the gut and mouth, and skin locations differed in their community assembly patterns. These results indicate that our microbiota, although personalized, varies systematically across body habitats and time: such trends may ultimately reveal how microbiome changes cause or prevent disease.

Soils harbor enormously diverse bacterial populations, and soil bacterial communities can vary greatly in composition across space. However, our understanding of the specific changes in soil bacterial community structure that occur across larger spatial scales is limited because most previous work has focused on either surveying a relatively small number of soils in detail or analyzing a larger number of soils with techniques that provide little detail about the phylogenetic structure of the bacterial communities. Here we used a bar-coded pyrosequencing technique to characterize bacterial communities in 88 soils from across North and South America, obtaining an average of 1,501 sequences per soil. We found that overall bacterial community composition, as measured by pairwise UniFrac distances, was significantly correlated with differences in soil pH (r ‫؍‬ 0.79), largely driven by changes in the relative abundances of Acidobacteria, Actinobacteria, and Bacteroidetes across the range of soil pHs. In addition, soil pH explains a significant portion of the variability associated with observed changes in the phylogenetic structure within each dominant lineage. The overall phylogenetic diversity of the bacterial communities was also correlated with soil pH (R 2 ‫؍‬ 0.50), with peak diversity in soils with near-neutral pHs. Together, these results suggest that the structure of soil bacterial communities is predictable, to some degree, across larger spatial scales, and the effect of soil pH on bacterial community composition is evident at even relatively coarse levels of taxonomic resolution.

The assessment of microbial diversity and distribution is a major concern in environmental microbiology. There are two general approaches for measuring community diversity: quantitative measures, which use the abundance of each taxon, and qualitative measures, which use only the presence/absence of data. Quantitative measures are ideally suited to revealing community differences that are due to changes in relative taxon abundance (e.g., when a particular set of taxa flourish because a limiting nutrient source becomes abundant). Qualitative measures are most informative when communities differ primarily by what can live in them (e.g., at high temperatures), in part because abundance information can obscure significant patterns of variation in which taxa are present. We illustrate these principles using two 16S rRNA-based surveys of microbial populations and two phylogenetic measures of community ␤ diversity: unweighted UniFrac, a qualitative measure, and weighted UniFrac, a new quantitative measure, which we have added to the UniFrac website (http://bmf.colorado.edu/unifrac). These studies considered the relative influences of mineral chemistry, temperature, and geography on microbial community composition in acidic thermal springs in Yellowstone National Park and the influences of obesity and kinship on microbial community composition in the mouse gut. We show that applying qualitative and quantitative measures to the same data set can lead to dramatically different conclusions about the main factors that structure microbial diversity and can provide insight into the nature of community differences. We also demonstrate that both weighted and unweighted UniFrac measurements are robust to the methods used to build the underlying phylogeny.Understanding differences in the composition of microbial communities is of major importance in microbial ecology. Advances in sequencing technology have allowed many microbial communities to be characterized using gene sequences amplified directly from environmental samples. However, methods for analyzing these sequences have lagged far behind the rate of data acquisition. Two important parameters of communities, including microbial communities, are ␣ diversity (the diversity within each sample, e.g., the number of species observed in an environment), and ␤ diversity (the partitioning of biological diversity among environments or along a gradient, e.g., the number of species shared between two environments) (Table 1) (31). Here, we focus on ␤ diversity, which can be measured in many different ways. These measures can be broadly divided into two categories: qualitative measures, which use the presence/absence of data to compare community composition, and quantitative measures, which also take the relative abundance of each type of organism into account (Table 1). Examples of commonly used qualitative measures of ␤ diversity include the Sörensen and Jaccard indices; quantitative measures include the Sörensen quantitative index and the Morisita-Horn measure (see reference 16 for a ...

Here we use published 16S rRNA gene sequences to compare the bacterial assemblages associated with humans, other mammals, other metazoa, and free-living microbial communities spanning a range of environmental conditions. The composition of the vertebrate gut microbiota is influenced by diet, host morphology and phylogeny, and in this respect the human gut bacterial community is typical for an omnivorous primate. However, a wider view reveals that the vertebrate gut microbiota is highly differentiated from free-living communities not associated with animal body habitats. The recently initiated international Human Microbiome Project should strive to include a broad representation of humans, as well as other mammals and environmental samples: comparative analyses of microbiotas and their microbiomes are a powerful way to explore the evolutionary history of the biosphere.

Background-The composition of the gut microbiome is affected by host phenotype, genotype, immune function, and diet. Here we used the phenotype of RELMβ Knockout (KO) mice to assess the influence of these factors.