The human microbiome: from symbiosis to pathogenesis

Abstract

The human microbiota is a complex assemblage of the microbes inhabiting many sites in the human body. Recent advances in technology have enabled deep sequencing and analysis of the members and structures of these communities. Two sites, the vagina and gastrointestinal tract, are highlighted to exemplify how technological advances have enhanced our knowledge of the host-microbiota system. These examples represent low- and high-complexity communities, respectively. In each example, certain community structures are identified that can be extrapolated to larger collections representing multiple individuals and potential disease or health states. One common feature is the unexpected diversity of the microbiota at any of these locations, which poses a challenge for relating the microbiota to health and disease. However, we anticipate microbiota compositional measurements could become standard clinical practice in the future and may become diagnostic for certain diseases or increased susceptibility to certain disorders. The microbiota of a number of disease states are currently being examined to identify potential correlations. In line with these predictions, it is possible that existing conditions may be resolved by altering the microbiota in a positive way.

Figure 1

Interindividual variation of the gastrointestinal microbiota. Distribution of bacterial phyla across 648 samples collected as part of the NIH Human Microbiome Project (HMP). Samples are arranged on the x-axis by abundance of dominant organism. The V3–V5 region of the bacterial 16S rRNA gene was amplified from total genomic DNA extracted from fecal samples and sequenced using Roche 454 pyrosequencing. Protocols and sample collection details are available at the Data Analysis and Coordination Center (DACC, http://www.hmpdacc.org/).

Figure 2

Intraindividual variation over time. Depending on the temporal scale, an individual's gastrointestinal microbiota can vary as measured using the overall community diversity measure, Shannon diversity (H). Data reconstructed from two individuals, male and female, left and right pie charts respectively. Size of pie sector indicates proportion of community; color represents dominant phylum; from Reference 78.

Figure 3

Measurements of the vaginal microbiota of two individuals representing a Lactobacillus-dominated community type and a diverse community type. Panels a and e are heatmaps that represent the presence or absence of the species at each sampled time point (represented on the X axis in panels d and h). Colors indicate the relative abundance, with yellow being absent and red being dominant. Panels b and f display the relative abundance of the phylotype at each time point. Panels c and g are measures of the diversity of microbiota, and panels d and h indicate environmental factors such as menses, sexual activity, and hygienic processes. The data clearly demonstrate a dynamic microbiota within the human vagina and highlight that diversity or stability cannot be determined by cross-sectional studies but only through frequent sampling of large cohorts. Additionally, diversity does not correlate with disease or impairment of function. These are representative data generated from the studies within the Ravel laboratory; further details of the study can be found in Reference .

Figure 4

Framework of interactions among the host, microbiota, and environment. Although these three features are discussed in the context of human homeostasis in this review, there are factors that interact independently of these primary features. All of these features are interacting in the environments (vagina and gastrointestinal tract) discussed in the text, each providing some perturbation in the system. This figure is not meant as an exhaustive list of features but only to illustrate the complexity of interactions that may affect measurements of the microbiota.

Figure 5

Two examples of the interaction of the microbiota, host, and pathogen. (a) Development of an antivirulence-signaling therapeutic (71, 80). The quorum sensing signal from the host microbiota and the hormone signals from the host are inhibited by a compound known as LED209. The inhibition of these signals prevents the activation of virulence factors, and the bacteria are removed through physical processes and/or the immune system. (b) Interaction of an incoming pathogen, Salmonella, and the host microbiota production of H₂S to inhibit other pathogens and provide a terminal electron acceptor for Salmonella. The production of these molecules provides an opening for the pathogen to colonize and cause disease (61).