The Basics: you and your normal flora, Part II

So, I left off on Tuesday noting two things about our normal flora: 1) that in the big picture, we know hardly anything about them; and 2) that one reason we know so little about them is because we've never grown many of them in a laboratory setting--that is, we've never cultured them using our typical tools of the trade.

What's one way to remedy this? Eliminate the need for culture, and take some cues from the microbial ecologists. More on this below.

I've mentioned the term "metagenomics" previously on this blog (see the stories about it here and here). Using this technique, samples are taken directly from the environment (*any* environment--a lake, soil, or your feces, for example), and the DNA is examined directly, without any enrichment methods such as culture. Therefore, you end up with DNA sequences for the entire population of organisms present--including brand-new organisms that haven't been previously studied.

These metagenomic analyses of microbes were first applied to environmental samples. One example found thousands of viruses in 200 liters of sea water. A 2004 study of the Sargasso Sea found DNA from nearly 2000 different species--including 148 types of unknown bacteria. Another study examined a biofilm growing in a pyrite ore, and found uncultured bacteria and archaea. These studies provide us with a wealth of new information on the organisms that are all around us, but we've never previously been able to examine. We can even clone portions of the DNA sequenced from these studies into well-characterized bacteria, in order to find out what it does--so that even if we've not yet been able to grow an organism carrying that gene, we can create one and learn about its function.

Similar methods have been applied to analyze the metagenome of the human body (including some of the links above). For example, a 2006 PLoS paper described the presence of pathogenic plant viruses in the human gut flora. The Institute for Genomic Research (TIGR) launched an initiative to similarly look at the oral bacterial metagenome:

In recent years, molecular methods have indicated that there are well over 400 species of bacteria in the oral cavity. But, so far, only about 150 of those species have been cultured in laboratories and given scientific names. Using a metagenomics sequencing strategy, TIGR scientists will be able to identify bits and pieces of the DNA of many of those oral microbes that so far have not been grown in labs and studied.

Additionally, just the other day the New York Times described new metagenomic research investigating our skin microflora:

The researchers determined that there were 182 species, belonging to 91 genera.

On average, each subject had about 50 species. But relatively few of them were shared with other subjects, and only four species were found on all six subjects. And when four of the subjects were tested again 8 to 10 months later, many of the original species had vanished, replaced by others.

At the genus level, the subjects were found to be different as well: only 6 of the 91 genera were found on all six subjects. But at a higher level of classification, phylum, the subjects had much in common: three phyla were found on all six subjects, and these accounted for about 90 percent of all species.

It's emphasized in that article, like I noted in the introduction, that even we microbiologists who study health and disease are wising up to the fact that microbial ecology affects us as well:

The skin is an ecosystem, and like larger ones it can change -- from winter to summer, or from being wrapped up to being exposed to light. "Our approach is becoming more and more ecological," he said.

So by taking an ecological approach to our normal flora, and looking at each different niche on our body as a place where a unique microbial ecosystem can flourish, we're finally starting to move beyond the "study bacteria in isolation" way of doing microbiology. True, this approach will remain important for a long time and still provides many important insights, but we need to move more toward an understanding of microbes in the context of their ecosystem, which includes not only their host but also the other resident flora that together make up the "human superorganism."

In the next part of the series, I'll discuss more about how we take this knowledge and apply it more specifically to studies of health and disease...stay tuned.

References

Breitbart et al.. 2002. Genomic analysis of uncultured marine viral communities. PNAS. 22:14250-14255. Link.

Tyson et al. 2004. Community structure and metabolism through reconstruction of microbial genomes from the environment. Nature. 428:37-43. Link.

Venter et al.. 2004. Environmental Genome Shotgun Sequencing of the Sargasso Sea. 304:66-74. Link.

Zhang et al. 2006. RNA Viral Community in Human Feces: Prevalence of Plant Pathogenic Viruses. PLoS Biology. 4(1): e3. Link.