members
Table 1. Features of the human gut microbiota and impact on human health Feature
Summary
Population density
In adults, levels of microbes increase with progression along the human GI tract. The stomach and small intestine are relatively sparsely populated (~106cells/ml luminal contents), with the distal colon harbouring the greatest concentration of microbes at 1013 - 1014 cells (1; reviewed in references 5 and 6).
Population structure and diversity
Comprised predominantly of bacteria, with methanogenic archaea forming major components in some individuals. Viruses, particularly bacteriophages, are also thought to be prominent members of this community. Eukaryotic microorganisms are present though less well characterized and thought to constitute relatively minor components. Bacteria: Low diversity at higher taxonomic levels with only 8 of the 55 known bacterial phylogenetic divisions well represented. Species derived from the Bacteroidetes and Firmicutes co-dominate with Actinobacteria and Proteobacteria forming comparably minor but significant fractions. Fusobacteria, Spirochaetes, Verrucomicrobi, and the candidate division VadinBE97 comprise the vast majority of the remainder. However, considerable diversity at the strain and species level is apparent with the adult gut microbiota estimated to contain ~150 to 800 distinct species. (References 2-5, 27). Archaea: Represented by only two species in the human gut microbiota: Methanobrevibacter smithii and Methanosphera stadmanae. However, in some individuals archaeal species, particularly M. smithii [L1], can account for a significant proportion of the total population (up to 10%). (References 2-5). Viruses: Initial metagenomic surveys indicated high viral diversity in this community, predominantly derived from bacteriophages, and detected ~1,200 viral genotypes (28). More recent surveys indicate much person to person variation and a potential dominance of a low number of high abundance virotypes (14).
Cultivability
Estimated that ~70 to 80% of bacterial species present in this community remain uncultured (5, 6, 27).
Stability and Inter-individual variation
Gut microbiota of healthy adults is generally considered both functionally and phylogenetically stable over time. However, considerable inter-individual variation is apparent, with each person believed to harbour their own distinct gut microbial community, both in terms of species present and the relative abundance of different bacteria. (2-4, 27, 29).
Gene-content
Due to the high gene density of prokaryotic genomes, the human gut microbiome is estimated to encompass a significantly greater gene complement than the human genome. Recent large scale metagenomic surveys identified 3.3 million unique genes from the gut microbiomes of 124 individuals, ~150 times larger than the gene set encoded by the human genome (3).
ecosystem. This naturally leads to questions regarding the activities encoded by the mobile metagenome, and how attributes of this flexible gene pool are involved in community development and function. A particular aspect of the gut microbiota that has been closely linked with HGT is the relative functional stability of this community over time in healthy adults (5, 6). Although this may be achieved through recruitment of member species with overlapping metabolic and functional profiles, HGT in the gut microbiota has been implicated as an important factor contributing to the development of a functionally stable community (15-18). In this case MGEs are thought to aid the dissemination of genes encoding core activities to a wide range of species in this ecosystem. This is thought to generate functional redundancy among community members, which guards against loss of key activities, and ensures continuity of important community functions (6, 9, 15). A key example of functional stability, achieved through HGT generated redundancy in this community, comes from studies of genes involved in 46
carbohydrate utilization, a major activity of gut microbes which salvages energy from the host diet (15) (Table 2). It has been estimated that up to 10% of our daily calories are derived from microbial fermentation of plant polysaccharides resistant to host digestive mechanisms (19), which recovers energy from the diet that is otherwise inaccessible to the human host. The ability of gut microbes to ferment such carbohydrates and release energy to the host in the form of short chain fatty acids, is distributed among a diverse array of species spanning the main bacterial divisions of the human gut microbiota (Bacteroidetes, Firmicutes, Actinobacteria, and Proteobacteria) (3, 5, 6, 13, 15, 16). While it is likely that some of this redundancy is the result of early events in the development of the gut microbiota, reflecting the recruitment of species capable of colonizing and utilizing available nutrients without harming the host, recent studies have also highlighted the role of HGT in the convergence and expansion of the required gene sets (15). Alternatively, studies of the Japanese gut microbiome have demonstrated how
MGEs can facilitate the acquisition of new abilities by the gut microbiota, which can benefit both host and microbe (13). Hehemann and coworkers recently demonstrated the acquisition of porphyranse and agarase degrading ability by the gut microbiomes of Japanese individuals (13). This was linked to the horizontal transfer of these genes from marine bacteria naturally colonizing dietary seaweeds (which are consumed without cooking), to members of the Japanese gut microbiota (13). Acquisition of these genes by gut commensals should permit the Japanese gut microbiota to utilize this dietary energy source, unlocking additional calories from the diet to the benefit of both host and microbe (13) (Table 2). In light of the potential for functional upgrades to this community that may be accessed through the mobile metagenome, it has also been proposed that a major role of this mobile gene pool may be as a conduit to the vast reservoir of genetic information extant in the wider prokaryotic world (9). Commensal and symbiotic microbes comprising the human gut microbiota are already becoming widely accepted as