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Deciphering the "Bugs" in Human Intestines

By John Roach
for National Geographic News
March 28, 2003
 
The human intestine is a swirling and churning environment that is host to microbial communities as diverse as those found in the Amazon rain forest. And like the regions beneath the soils that carpet the rain forest floor, much of what lies within the gut remains unexplored.

A series of papers in the March 28 issue of Science delves into this scientific frontier and begins to unravel the secrets of the complex and highly evolved microbial communities that teem throughout the length of our intestines.



The human gut is home to at least 500 species of microbes. The number of bacterial cells may exceed the number of human cells our body. Some microbes are firmly rooted in place. Others are just tourists on a leisurely stroll through the gastrointestinal tract. The residents form communities that are dense and bursting with pockets of ethnic pride.

Their collective role is to process food and fight off disease, but like the complexity of the microbes that process nutrients in the forest floor, scientists are just beginning to understand the contribution of each species and identify what makes some of them go bad.

One of the papers in Science reveals the genetics of a dominant gut bug that serves humans well by breaking down otherwise indigestible food. Another paper details the inner workings of a normally benign bug that has evolved drug-resistance and turns traitor when its human host is weakened by disease.

These studies are a positive step towards revealing "the underlying basis for the highly coevolved relationship between humans and microbes," write Michael Gilmore and Joseph Ferretti of the University of Oklahoma Health Sciences Center in Oklahoma City, in an accompanying perspective article.

The Good Bug

One common bacterium in the human digestive system is Bacteroides thetaiotaomicron. Jeffrey Gordon, a molecular biologist with the Washington University School of Medicine in St. Louis, Missouri and his colleagues plumbed the bacterium's genetic material to find out what it does.

They discovered that much of the bacteria's genome, which is one of the largest examined, is dedicated to breaking down complex carbohydrates that enzymes in the human gut cannot otherwise process. The complex carbohydrates are called polysaccharides. They are common to foods such as vegetables and other plant materials.

The human host benefits, explained Gordon, because B. thetaiotaomicron also breaks down the polysaccharides into products that can then be absorbed by the body. "We absorb 15 to 20 percent of daily caloric intake this way," he said.

The bacteria also exhibit an elaborate environment-sensing system to help them thrive in the highly competitive community within the human digestive system.

In order to be successful in the gut where there are literally trillions of bacteria competing for the nutrients their human host eats, the successful microbe must develop a system to determine what nutrients to go after and a strategy to capture them. B. thetaiotaomicron, says Gordon, has learned how to do this with great facility.

"This organism has an enormous capacity to grab the polysaccharides it encounters from our diet," he said. "It senses their presence and deploys the proper set of enzymes to harvest these nutrients as they enter its niche. This is beneficial to them, to other members of the gut's microbial community, and to us."

Bug Gone Bad

The bacterium Enterococcus faecalis is a relatively minor player in healthy human hosts and scientists can't say for sure what it does. "We don't know whether it's beneficial or whether it's just neutral in its interaction," said Ian Paulsen, a researcher at the Institute for Genomic Research in Rockville, Maryland.

But when the host becomes ill, new strains of the microbe have evolved an uncanny ability to attack the weakened immune system with fierce resistance to even the most potent of antibiotics, causing a range of maladies such as the heart disease infective endocarditis and urinary-tract infections.

Doctors often treat E. faecalis infections with the potent antibiotic vancomycin if other drugs fail to slow the infection's progress. But now there are more and more strains that have evolved resistance to the drug, making it more difficult for doctors to effectively treat infections.

Paulsen and his colleagues at the institute sequenced the genome of a strain of the bacterium that has developed a resistance to vancomycin. They discovered that more than a quarter of its genome consists of mobile, or foreign, DNA.

"They are bits of DNA that can move around, that can hop between different bacterial strains and species," said Paulsen. The drug resistance is found in the mobile DNA.

For this particular strain, the researchers identified two sites on the genome that are related to vancomycin resistance. These encoded genes allow the bacterium to alter its cell wall structure to prevent the drug from causing any damage.

Paulsen is not sure how the knowledge of this particular strain applies to the wider population of E. faecalis, but he does say that it gives researchers some information they can use to ask more focused questions on how best to treat E. faecalis infections.

"Having the genome doesn't give you all the answers to these sorts of problems," said Paulsen. "But it enables experiments and technologies to start trying to answer these questions."
 

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