Biodiversity and functional genomics in the human microbiome

Abstract

Over the course of our lives, humans are colonized by a tremendous diversity of commensal microbes, which comprise the human microbiome. The collective genetic potential (metagenome) of the human microbiome is orders of magnitude more than the human genome, and it profoundly affects human health and disease in ways we are only beginning to understand. Advances in computing and high-throughput sequencing have enabled population-level surveys such as MetaHIT and the recently released Human Microbiome Project, detailed investigations of the microbiome in human disease, and mechanistic studies employing gnotobiotic model organisms. The resulting knowledge of human microbiome composition, function, and range of variation across multiple body sites has begun to assemble a rich picture of commensal host-microbe and microbe-microbe interactions as well as their roles in human health and disease and their potential as diagnostic and therapeutic tools.

Figure 1. Overview of bioinformatic methods for functional metagenomics

Microbial community samples typically contain many species of bacteria and other microorganisms, here indicated by different colors. After total DNA has been extracted, the composition of the community is determined by amplifying and sequencing the 16S rRNA gene. Highly similar sequences are grouped into Operational Taxonomic Units (OTUs), and these OTUs are labeled by comparison with databases of recognized organisms. OTUs can then be analyzed in terms of presence/absence, abundance, or phylogenetic diversity. In order to determine biomolecular and metabolic functions present in the community, the total metagenomic DNA may be sequenced and compared with function-oriented databases. Alternatively, sequenced community DNA can be compared to reference genomes. This allows identification of microbial sequence variants and polymorphisms, as well as provides an alternative means of detecting the presence and abundance of specific organisms. In the future, the emerging fields of metatranscriptomics, metaproteomics, and metametabolomics will help build an integrated picture of gene expression and interactions in microbial communities.

Figure 2. A map of diversity in the human microbiome

The human microbiome is dominated by four phyla: Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. In the center is a phylogenetic tree of organisms abundant in the human microbiome. Commensal microbes are indicated by circles, and potential pathogens are indicated by stars. The middle ring corresponds to body sites at which the various taxa are abundant and is color-coded by site (e.g., Ruminococcus (blue) is found mostly in the gut, whereas Lactobacillus (purple) is found mostly in the vagina). The bar heights on the outside of the circle are proportional to taxa abundance at the body site of greatest prevalence (e.g., Streptococcus mitis (yellow) dominates the inside of the cheek, whereas the gut is abundant in a variety of Bacteroides). The intensity of external colors corresponds to species prevalence in each body site. Data from the Human Microbiome Project [11] and MetaPhlan [79], and microscopy images from BacMap [80].