What Will Human Microbiome Metagenomics Tell Us?

NIH, in about six months, will release a huge sum of money to fund the study of the human ‘microbiome’: those microorganisms that live on or in us. One of the things that will be done with this money is meta-genomics which is “the study of genomes recovered from environmental samples as opposed to from clonal cultures.” (In this case, the samples would be fecal, vaginal, your mouth, etc.). In other words, we can sample the ‘community’ of genomes (or perhaps we should call it the community ecology of genomes). So I have a question: what do we learn from meta-genomics of the human microbiome?

Let me explain what I mean by this. There are lots of useful things that come from meta-genomics. First, organisms that we currently can’t culture will be discovered. Second, having some knowledge of genomes can help us develop better methods for tracking in situ community dynamics and interactions. Currently, most studies amplify 16S RNA genes and use them as a ‘barcode’ to follow species abundances. We could develop better markers (i.e., ecologically relevant genes) and build better technologies to study the human microbiome. We could also follow community-level gene expression patterns (which would be really useful). The list of tools and methods stemming from this could go on and on.
What I’m asking, however, is what do we learn from meta-genomics per se about the ecology of the human microbe that we wouldn’t be able to glean from genetic barcodes, or for that matter, latin binomials?
In other words, if we sequenced enough human microbiomes (e.g., fecal samples from 200 people), and enough genomes per sample to develop the tools and methods I described above (and many others I didn’t), would there be any need to sequence additional genomes? What exactly could we learn from the ecology of genomes?

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3 Responses to What Will Human Microbiome Metagenomics Tell Us?

  1. Chris says:

    Off the top of my head: You can’t identify new SNPs or indels using genetic barcodes. When barcoding, you limit yourself to a specific subset of genes. In order to find novel mutations in the rest of the genome, you have to actually sequence the DNA.
    Preselecting a set of genes to study will be fine for many applications, but others might require searching the meta-genome for novel features. Given the high mutation rate of bacteria, I don’t think you’ll ever be able to say that sequencing is no longer useful in that context.

  2. Paul Orwin says:

    The interesting thing will probably not be “barcoding”, which has been done at least with the gut microbiome. This has yielded lots of interesting things, but the new fad is shotgun metagenomics and functional metagenomics, where you just sequence lots of random DNA from a source (or maybe cDNA recovered from environment derived RNA) to learn about the functional characteristics of the environment. The “cool” example is Ventner’s Sargasso Sea project, but others are doing this too. It is likely that new enzymes for degradation and metabolism will be identified. The work pointing to gut microbe influences on obesity, and on archaeal pathogens in periodontal disease suggest that we have a lot to learn about our microflora, and that non-culture techniques can add a lot besides a census.

  3. The EU-funded project MetaHIT (Metagenomics of the Human Intestinal Tract) has an official website available at: http://www.metahit.eu

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