Human Gut Microbes Sequenced

ROCKVILLE, MARYLAND (07/27/06) - If you're sitting in a room by yourself, don't think you're alone. You have the company of trillions of microbes living in your gut and other parts your body. And now, the genomes of the ones living in your gut have been sequenced via a metagenomics approach. The sequencing is the first step in helping researchers identify just what role bacteria play in the gut, and in human health in general.

Be assured, microbes living in the gut are not a bad thing, said Steven Gill, PhD, associate professor at the Center of Excellence in Bioinformatics and Life Science, SUNY, Buffalo. Dr. Gill was previously with The Institute for Genomic Research (TIGR) in Rockville, Maryland and was lead author of a metagenomics analysis of microbes in the human gut published in the the June 2, 2006 issue of Science.

Some of these microbes are known to provide functions such as helping the body with digestive processes. For instance, people don't make the enzymes and proteins necessary to break down certain components of plant fibers. "If we ate them without the bacteria in our gut we wouldn't be able to digest them. But the bacteria that are present in our gut do make the enzymes that are capable of breaking down that plant material," he said. In addition, it's bacteria in the gut that produce certain vitamins such as B1 and B6 that we can't produce ourselves, he said.

Isolating and sequencing individual microbes from the human gut was too daunting a task on its own, considering there are 10 to 100 trillion different kinds. Instead, a metagenomics approach was used.

"Metagenomics means sequencing massive numbers of bacteria at one time. In this case you take this microbiota, which is a mixed community of bacteria, and you extract all the DNA from that community. That DNA represents genomes from every bacterium in that population." Dr. Gill said. In brief, researchers take samples of the entire community of micro-organisms and mush them up together, then perform the sequencing of the entire lot together.

High quality genetic sequences were attained from microbes obtained from fecal samples provided by two healthy volunteers, a woman and a man. A total of 65,059 sequences were obtained from the woman, and 74,462 from the man. Because of technical limitations, not all the sequences were of high enough quality to analyse, accounting for the difference in numbers between the two subjects. The sequences are being compared to databases of known microbial DNA databases to try to figure out what the gut microbes do.

Microbes are essential to human survival, performing tasks that the human body on its own can't. This means the human body is more of an amalgam of different life forms rather than being a lone organism. It is believed that microbes co-evolved with humans, with each supporting the other's survival.

Interestingly, other research suggests people are not born with microbes, but pick them up from their environment. Infants get them from breast feeding (they are present on the mother's skin), and from the food we eat (some microbes hitch rides on meat and vegetables).
Because of microbes' strong link to what constitutes a human body, "some people liken (the sequencing of human microbes) to the second human genome project. Now the next step is to do the genomes of the bacteria that live on us -- such as on our skin," he told Access Excellence in a interview.

"We know that microbial flora plays a significant role in human health and disease and we want to find out what that role is in different situations. This project is a first step that's looking at what's there in a healthy person," he said.Communities, or biomes, of microbes also live on our skin, in our nose, in our ears, and other parts of the body.

There is also a shift in thinking about the role of microbes. Whereas it was thought that individual microbes performed specific tasks on their own, there is now thought that some of them may even work together. Evidence suggests that signals are transmitted between some groups of microbes. In addition, microbial flora populations can vary between individuals. For instance, there are differences in the flora between vegetarians and non-vegetarians; older people and younger people; and healthy people and people with conditions such as ulcers or colon cancer.

"The next step is to look at people of different ages with different diseases, and go through the list of possibilities and see what their microbial populations are like," he said. Once what specific microbes do to help human health is better understood, it could open doors to new types of treatments for conditions such as irritable bowel disease, Crohn's disease, and more. Microbes may even provide needed functions researchers haven't thought of, and the presence of either too many or not enough of certain micbroes may contribute to human diseases.

Intriguingly, along with 70 divisions of bacteria found to be living in the human are 13 divisions of the more primitive Archaea. Archaea are recognized as one of the earliest life forms on the planet, with many being known to live in extreme environments such as deep sea thermal vents, and in chemically hostile environments. It is not yet known what role the Archaea play in the human gut.

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Related information on the Internet

Metagenomics article. DOE Joint Genome Institute, US Department of Energy.

Bacterial flora in humans. Todar's Textbook of Bacteriology.

General background on biodiversity and metagenomics. University of British Columbia.

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