Intestinal bacteria have crucial roles beyond digestion

Gut reactions

12:35 PM CDT on Thursday, September 4, 2003

By SUE GOETINCK AMBROSE / The Dallas Morning News

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We are not alone.

Billions upon billions of beings live, eat and die among us, unseen, unfelt, unnoticed.

These aren't extraterrestrials that have invaded Earth. These are intraintestinals, and they've invaded our guts.

The intraintestinals are microbes – mostly bacteria – that live deep inside the human intestine.

"We walk around as host to a microbial nation," says Jeffrey Gordon, a molecular biologist at Washington University School of Medicine in St. Louis.

Scientists have known for decades that the tiny gut dwellers help break down food that would otherwise go unused. But now researchers are finding that some of these bacteria have many other talents, including helping the intestine develop and defending against harmful germs. The bacteria may even make foods more fattening for some people.

Nobody has done an exact count, but some estimates suggest that as many as 100 trillion microbes from at least 500 distinct species live inside the intestine of the average adult.

That many microbes shouldn't be ignored, scientists say.

"There are 10 times more bacterial cells in your gut than there are [cells] in your body," says Lora Hooper, a molecular biologist at the University of Texas Southwestern Medical Center at Dallas. "They must be doing something important."

One recent study shows that microbes actually trigger formation of blood vessels in the intestine after birth. Another report documents how a species of "good" bacteria helps intestinal cells make chemicals that can poison "bad" bacteria.

But while the bacteria provide much-needed services, even the most well-intentioned guest can be a nuisance. In some cases, the "good" bacteria are unwitting accomplices in making "bad" bacteria immune to antibiotics. In other instances, these normally considerate gut-dwellers can trigger inflammation, leading to colitis or Crohn's disease.

Scientists say that studying this microbial nation will yield new insights into how the body functions, in sickness and in health. A better grasp of how the bacterial community operates could help prevent the troubling side effects of antibiotics. Researchers might also be able to turn the use of probiotics – bacterial concoctions aimed at restoring the gut's microbes – from guesswork into science.

Some scientists even suspect that gut microbes may dictate how many calories are absorbed from food. If that's the case, a slice of cake could be more fattening to someone who harbors an unfortunate mix of bacteria.

And the microbes may also be producing compounds useful as medications. "Understanding their strategies may provide us an entirely new class of compounds for enforcing our health or preventing or treating disease," Dr. Gordon says.

Obstacle to study


Only 50 years ago, scientists didn't even realize that most of the microbes in the intestine were alive. Researchers had examined fecal samples under the microscope and noticed bacteria in huge numbers – as many as 100 billion bacterial cells per gram of fecal material. But when transferred to lab dishes, the cells did nothing.

"You had something that didn't grow and didn't move, so they must be dead," says Lillian Moore, a retired microbiologist from Virginia Tech University and one of the pioneers of gut bacterial research.

Actually, the bacteria were very much alive. They just had an intense dislike for oxygen, which is almost absent inside the intestine and way too abundant in standard laboratory growth chambers.

So in the 1960s, Dr. Moore and her late husband, Ed Moore, turned to the oxygen-free techniques originally developed to study the digestive processes in the rumen of cattle. Now comfortably settled in a home away from home, the bacteria thrived. The Moores realized that there were hundreds of species thriving inside every healthy person.

These species begin their journey into the gut at birth and don't ever stop. Bacteria coat food, skin and everyday objects, all of which come into contact with the hands or mouth.

"I don't care how clean you think you are," says Abigail Salyers, a microbiologist at the University of Illinois at Urbana-Champaign. "You get bacteria on your hands and that is reintroduced into your mouth or your nose.

"From about three minutes after you're born, and even after you're dead, they're part of your person whether you like it or not."

From the mouth, the bacteria travel through the stomach and then nestle in the small and large intestines. Different species tend to settle in different regions along the length of the gut. But because it's tricky to isolate the bacteria, scientists haven't taken a good census of the numbers and types of organisms.

"We don't know really very thoroughly what's there," says Dr. Kenneth Wilson, an infectious disease specialist at Duke University and the VA Medical Center in Durham, N.C. "There's got to be a huge amount of stuff going on that we just don't have any inkling of."

Even without a precise count of these microscopic residents, scientists do know that each gut is unique.

"Each person has his or her own individual fecal flora and maintains it over long periods of time," says Dr. Moore.

Scientists don't know why bacterial populations are so personal. Diet, genetics and the environment could all play a role. For instance, breastfed and bottle-fed infants have different proportions of certain bacteria. And genetically identical twins' microbial populations appear more similar than those from unrelated people or even spouses.

Although bacteria in the gut are part of every human being, researchers have concentrated more on bacteria that cause disease.

"That's understandable," says Illinois' Dr. Salyers. "You tend not to focus on the things that are possibly good for you."

Intestine builders


But without these good bacteria, life would be pretty bad. In 2002, Drs. Hooper and Gordon reported on a study of mice grown in a germ-free laboratory. The natural invasion of bacteria into the mice's digestive tract never happened. And as a result, the mice's intestines didn't mature properly, the scientists reported in the Proceedings of the National Academy of Sciences.

Normally, when mice are born the blood vessels that absorb nutrients in the small intestine haven't fully blossomed. But without microbial visitors, "the number of blood vessels in the gut is smaller," Dr. Gordon says. "The absorptive capacity is less."

After exposure to gut bacteria, the blood vessels matured within 10 days.

In fact, studies from the 1980s showed that rats raised in germ-free conditions have to take in almost 20 percent more calories than normal mice to maintain their body weight. Scientists suspect the extra calories are needed because the rodents aren't getting any help with food digestion from the bacteria. And the new study offers another possibility – that poorly developed blood vessels may also be increasing the need for calories.

Killing invaders


Not only do good bacteria break down food and help the intestine mature, they also seem to protect it from harmful bacteria. In a report published this year in the journal Nature Immunology, Drs. Hooper and Gordon showed that a microbe in the gut triggers the production of a chemical that can kill other bacteria.

The gut bacteria Bacteroides thetaiotamicron (known as B. theta for short) sends a message to intestinal cells telling them to produce an antibacterial protein called Ang4, Dr. Hooper says. The protein is especially good at killing a class of bacteria that aren't a big part of the normal gut population. So by telling its host to produce the antibacterial compound, B. theta may be ensuring that the right bacteria thrive in the gut, Dr. Hooper says.

The Ang4 compound may also provide an "electric fence" that shields the intestinal cells from microbes that can trigger inflammation, Dr. Hooper says. Abnormal reactions to bacteria that result in inflammation are thought to be at the root of inflammatory bowel diseases.

Researchers say they're just beginning to appreciate everything the gut's bacteria do. Since humans depend on bacteria to digest certain foods, Dr. Gordon says he suspects it's easier for some people to absorb calories, depending on which bacteria are living in their gut. He is testing the idea in his lab. If he's right, the bacteria in the gut could influence how fattening or nutritious food is for different people.

Other scientists, including Dr. Salyers, have found that the normally helpful gut bacteria may be passing out genes that make other microbes immune to antibiotics. And, she says, more research is needed to understand probiotics, cocktails of bacteria touted to restore the gut's inhabitants to a healthy state.

"The problem is that the probiotics that are currently being sold are based on a lack of knowledge," Dr. Salyers says. "The products out there, in my opinion, are pretty much useless."

Dr. Salyers and her fellow scientists hope their work will give bacteria a better image. The relationship between humans and their microbial friends has evolved through millions of years of coexistence. And since humans acquire bacterial friends from our surroundings, the researchers say, people should ease up on their quest for perfect cleanliness. Dirty is OK.

"Pig-Pen had it all right," Dr. Gordon says. "That's the natural state of being in our world."

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