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Gut Check - The bacteria in your intestines are welcome guests
05/10/04 01:33 PM
Gut Check - The bacteria in your intestines are welcome guests
New York and London are famous for both their congestion and the diverse origins of their residents. But if you're looking for the ultimate teeming metropolis of immigrants, check out the large intestine. In people, some 500 to 1,000 kinds of bacteria reside in this part of the gastrointestinal (GI) tract, and these gut microbes outnumber all the cells in your body, perhaps by as much as a factor of 10.
"The density of this society is mind-boggling," says Jeffrey I. Gordon of Washington University School of Medicine in St. Louis.
It's a society overlooked by most microbiologists, who generally stick to the myriad bacteria that cause disease. Yet some scientists argue that it's shortsighted to ignore what they call the microflora living in our intestines.
"What these bacteria do definitely makes a very significant contribution to our health—or lack thereof," says Mark Schell of the University of Georgia in Athens, who studies an intestinal microbe called Bifodobacterium longum.
Shell and a few other researchers have recently begun to probe exactly what individual microbes do for or to the intestine.
Consider Bacteriodes thetaiotaomicron. Although not as well known, it's more than 1,000 times as abundant in the guts of people and mice as the extensively studied bacterium Escherichia coli. Some researchers have proposed that in return for a steady food supply, B. thetaiotaomicron breaks down indigestible complex carbohydrates into easily absorbed sugars and produces other substances, such as vitamins, that benefit its host.
There may be much more to this microbe-host relationship, however. About a decade ago, Gordon chose B. thetaiotaomicron as a prototypical germ for studying how microbes influence the GI tract. This bacterium normally becomes a predominant member of the intestinal community about the time an animal is weaned from its mother's milk. Gordon's research team has discovered that the microbe can turn on specific intestinal genes, promote the growth of blood vessels necessary for the gut's function, and trigger production of a chemical that may kill competing bacteria. Investigators are now asking just how much gut bacteria regulate the developing and adult human body.
"Bacteria do an awful lot for us and with us," says Gordon. "Most people's views of bacteria are of menacing, disease-promoting entities. Au contraire, I think that most of our encounters with bacteria are mutually beneficial, friendly, and part of our normal biology. . . . They've insinuated themselves into our biology and coevolved with us."
Perhaps the best way to understand the significance of intestinal microorganisms is to see what happens when an animal doesn't have them. During the past 50 years, researchers have created germfree mice and rats by delivering the animals by cesarean section into sterile environments and maintaining them there. "It's a very demanding technology," says Gordon. Scientists have generally used such germfree animals to study how particular pathogens cause diseases.
One of the most striking aspects of a germfree rodent is that it must consume about 30 percent more calories to maintain its body weight than a typical rodent does. Germfree animals are also unusually susceptible to infections, presumably because the microflora in a normal gut ward off foreign pathogens.
As a way to study animals hosting a simplified society of gut bacteria, Gordon and his colleagues have introduced B. thetaiotaomicron into germfree mice. Their first significant discovery was that the bacterium could change what sugars the intestine makes.
The surfaces of intestinal cells of typical mice are coated with complex sugars containing the simple sugar fucose and B. thetaiotaomicron consumes the fucose for energy. In germfree mice, however, fucose production ceases around the time of weaning.
If B. thetaiotaomicron colonizes a germfree mouse before weaning, however, normal fucose synth