The human microbiome: our second genome

Abstract

The human genome has been referred to as the blueprint of human biology. In this review we consider an essential but largely ignored overlay to that blueprint, the human microbiome, which is composed of those microbes that live in and on our bodies. The human microbiome is a source of genetic diversity, a modifier of disease, an essential component of immunity, and a functional entity that influences metabolism and modulates drug interactions. Characterization and analysis of the human microbiome have been greatly catalyzed by advances in genomic technologies. We discuss how these technologies have shaped this emerging field of study and advanced our understanding of the human microbiome. We also identify future challenges, many of which are common to human genetic studies, and predict that in the future, analyzing genetic variation and risk of human disease will sometimes necessitate the integration of human and microbial genomic data sets.

Figure 1

Workflow for metagenomic sequencing and analysis projects.

Figure 2

Genus- and phylum-level classification of bacteria colonizing a composite subject, showing that human microbiome diversity is dependent on the site sampled. Sites in the oral cavity share greater similarity than other types of sites, such as the skin, vagina, and gut. Data derived from the NIH Human Microbiome Project study (http://commonfund.nih.gov/hmp).

Figure 3

Interpersonal variation in levels of bacteria (classified at the genus and phylum levels) of the skin, vagina, gut, and mouth. The median relative abundance of each bacteria is indicated by a central point, the boxes extend from the first to third quartiles, and the whiskers extend to the highest and lowest data points no farther than 1.5 times the interquartile range from the box. Gray dots represent individual samples that lie outside this range. Each body habitat harbors dominant signature taxa. Actintobacteria (Corynebacterium and Propionibacterium), Firmicutes (Staphylococcus, Streptococcus, and others), and Proteobacteria predominate on the skin, with interindividual variation displayed; Lactobacillus predominates in the vagina; Bacteriodetes and Firmicutes predominate in the gut; and Bacteriodetes, Firmicutes (Streptococcus), Fusobacteria, and Proteobacteria predominate in the mouth. Data derived from the NIH Human Microbiome Project study (http://commonfund.nih.gov/hmp).