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Researchers blame bacteria for intestinal disorder

(Republished with permission from the St. Louis Post-Dispatch. This article originally ran in the Science & Medicine section on Thursday, July 21, 2005)

By Tina Hesman Of the Post-Dispatch

It's a refrain that would make Madonna proud.

"We are living in a microbial world," Jeffrey I. Gordon practically sings out.

And by Gordon's estimate, the Material Girl is actually a microbial girl. All people are composed of more microbes - bacteria and an ancient form of single-celled life called Archaea - than human cells. For every human cell in the body, 10 microbes inhabit the intestinal tract, said Gordon, the director of the Center for Genome Sciences at Washington University.

And when our intimate relationship with our inner bacteria goes wrong, it's enough to make people sick, according to a controversial new theory about the cause of irritable bowel syndrome.

About 15 percent of people suffer from the intestinal disorder known as IBS, also called spastic colon, mucous colitis, spastic colitis, nervous stomach or irritable colon. The disease is characterized by abdominal pain, diarrhea or constipation or both with bloating and gas and a host of other problems that make its sufferers miserable and can interfere with normal life.

"It pretty much disables your life," said Jennifer Freese, 37, a dental assistant from Waterloo. She has suffered from irritable bowel syndrome since she was 19, Freese said. Freese's workday was often interrupted by as many as 15 bathroom visits. She bloats so much after eating that she changes pants size, she said.

Freese has tried remedies galore to counteract the disease, which often leaves her fatigued and feeling as if she has the flu.

Doctors used to think the disease was a result of nerves and stress. The notion arose largely because modern medicine has been hard-pressed to find a cause. Lacking physical evidence, doctors often assumed the problem was in the patient's head, said Dr. Mark Pimentel, co-director of the GI motility program at Cedars Sinai Medical Center in Los Angeles.

"Anything we don't understand, we chalk up to stress. Coronary heart disease - heart attacks - used to be attributed to a type-A personality. You never hear about that anymore," Pimentel said.

Now doctors and scientists are thinking that soured relations with the microbial communities living inside us might account for irritable bowel disease and other problems.

Pimentel and his colleague Dr. Henry C. Lin theorize that the problem is in the small intestine. Bacteria from the colon might invade the normally microbe-free small intestine and set up shop. The invasion triggers the immune system to make chemicals that might interfere with nerves and cause irritable bowel symptoms.

The microscopic denizens of the colon (also known as the large intestine) form an organ within an organ that is essential for proper health, scientists say. Some bacteria detoxify cancer-causing chemicals. Microbes help extract nutrients from food and signal hosts when to make and store fat, the researchers have found.

Each meal a person eats is like "dining in with 10 trillion friends," Gordon says.

And that's fine as long as the guests are invited to dinner and sit in their designated spots, said Lin, now an associate professor of medicine at the University of Southern California's Keck School of Medicine.

"These are not good or bad bacteria. These are your bacteria. They just happen to be in the wrong place," Lin said.

People with irritable bowel syndrome actually excrete 400 times more gas, mostly methane and hydrogen, than well people, but only after eating, Lin said.

The gas-bag culprits are most likely bacteria that got into the small intestine and stayed because cleaning contractions of the organ failed to clear the microbes, Lin said. After a meal, the microbes feast and give off gas that leads to bloating and tummy rumbles.

Lin and Pimentel developed a simple breath test that doctors can use to diagnose possible bacterial overgrowth in the small intestine. Some local doctors and hospitals are beginning to use the test.

Freese and a handful of other people with the syndrome sat in a room at the Creve Coeur office of Dr. Leonard Weinstock and his partners at Specialists in Gastroenterology this week. She was there for a breath test to determine whether she might have excess bacterial growth. In Freese's hands were a blue plastic bag with a mouthpiece, a timer and a book. Other patients were outfitted similarly.

Weinstock's assistant, Leslie Hilliard, tore open a package of lactalose, an indigestible (for humans) sugar, and stirred the powder into water in a plastic foam cup. Freese drank the sugar solution and sat back to read as her timer counted down 15 minutes. When the timer sounded, Hilliard fitted a syringe to the side of Freese's blue bag. Freese lifted the contraption to her lips and exhaled, raising a finger as the last of the breath left her lungs. Hilliard drew off the air into the syringe and injected it into a machine that analyzes the composition of gases in the breath.

Freese would spend the next two hours in the doctor's office, breathing into the blue bag at 15-minute intervals. An early jump in the amount of hydrogen or methane in Freese's breath could indicate that her small intestine was overgrown with bacteria. About 70 percent of his patients with irritable bowel syndrome have abnormal breath tests, Weinstock said. Other doctors and researchers have reported that about 40 percent to more than 80 percent of patients with the syndrome breathe evidence of bacterial overgrowth when given lactalose.

When Weinstock finds abnormal breath test results in a patient with the syndrome, he prescribes an antibiotic and a drug to restore bowel contractions. Pimentel devised the therapy, known as the Cedars Sinai protocol. Results of a clinical trial with the therapy are not yet published, Pimentel said.

Weinstock said he is sold on the usefulness of the technique, but other doctors are not entirely convinced that bacteria in the small intestine are the problem.

"I consider this preliminary, very exciting information," said Dr. Charlene Prather, a gastroenterologist at St. Louis University. "But it's not the panacea to cure all IBS, nor is it the cause of all IBS."

It's hard to prove any particular therapy works to relieve irritable bowel symptoms, Prather said. That's because patients are almost as likely to respond to placebo treatments as they are to medications.

So far, other researchers have not upheld the California researchers' theory, said Dr. Chandra Prakash, a gastroenterologist at Washington University School of Medicine.

He and others say many of the symptoms seemed to be triggered by a miscommunication between the bowel and the gut and probably have neurological triggers, Prakash said. But bacterial overgrowth might be a component.

The theory has not yet been adequately tested, said Dr. Arnold Wald, director of the gastroenterology fellowship training program at the University of Pittsburgh Medical Center. The breath test measures gas production for a two-hour period following drinking a sugar solution. But no one has yet proved that the sugar only reaches the small intestine during that time.

"Their theory is novel and provocative, but, in my opinion, they've not yet proven it," Wald said.

But the idea offers researchers a fresh perspective on previously enigmatic diseases, some doctors say.

"If corroborated, it will change the way we look at diseases like irritable bowel," Prakash said.

Reporter Tina Hesman E-mail: thesman@post-dispatch.com Phone: 314-340-8325

Copyright 2005 St. Louis Post-Dispatch, Inc.

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Jeffrey I. Gordon
The Dr. Robert J. Glaser Distinguished University Professor and Director, Center for Genome Sciences and Systems Biology
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