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 synthesis continues throughout life, the researchers found. Through a still undiscovered signal, the microbe apparently induces the intestinal cells to make one of its favorite foods. The bacterium even has a fucose sensor that informs it when this food source is scarce, according to Gordon and his colleagues.
The capacity of B. thetaiotaomicron to instruct intestinal cells to make fucose was just a hint of things to come. To get a more comprehensive picture of the bacterium's influence, Gordon's group turned to microchip-size devices, called DNA microarrays, that monitor the activity of thousands of genes at once (SN: 3/8/97, p. 144).
With such instruments, the scientists took a snapshot of the gene activity in the mouse intestine. By comparing tissue from germfree mice and mice hosting B. thetaiotaomicron, the team found that the presence of the bacterium significantly reduces or boosts the activity of about 100 of the approximately 25,000 rodent genes in the microarray survey.
Some of the intestinal genes triggered by the microbe help mammals absorb and metabolize sugars and fats, Gordon and his colleagues reported in 2001. Other activated genes fortify the cellular barrier that prevents bacteria, both dangerous and friendly, from sneaking out of the intestine into other tissues and the bloodstream. And yet other affected genes determine how the intestine detoxifies compounds and how the gut matures.
"We were amazed at the breadth of normal intestinal functions affected by a single microbe," says study coauthor Lora V. Hopper. Gordon adds, "It's difficult to anticipate the full range of host functions that might be manipulated by these microbes."
The genetic activity that the researchers didn't see in the bacteria-colonized mice was interesting, too. Even though the originally germfree mice had never encountered B. thetaiotaomicron before, there was no increase in activity of the genes underlying an immune or inflammatory response. That's a reflection of the microbe's still mysterious skill at convincing a host tha