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E. Coli Linked to Inflammatory Bowel Disease

Immune response to bacteria may lead to chronic irritation

TUESDAY, Feb. 5, 2002 (HealthDayNews) -- An intestinal infection caused by strains of a common bacterium may be linked to the development of inflammatory bowel disease, a new study says.

French researchers report that a heightened immune interaction between Escherichia coli and the cells lining the intestine may result in the symptoms experienced by people with inflammatory bowel disease (IBD). They suggest their work indicates antibiotics might be a useful tool when treating IBD.

The findings appear in today's issue of the Proceedings of the National Academy of Sciences.

IBD refers to a group of conditions that cause inflammation of the intestinal tract. The group includes Crohn's disease, irritable bowel syndrome and ulcerative colitis.

Symptoms of these disorders include changes in bowel habits, particularly diarrhea, as well as abdominal pain, fever, joint pain and skin lesions.

IBD affects approximately 2 million Americans, with symptoms generally appearing in a person's 20s or 30s. There is evidence that a predisposition to these conditions can be inherited, with the diseases being particularly common in people of eastern European and Jewish descent.

A research team led by Dr. Antoine Toubert suggests that in genetically susceptible people, the immune system's response to bacteria could trigger the inflammation associated with these diseases.

Toubert, an associate professor of immunology and histocompatibility at the Hôpital Saint-Louis in Paris, studied this response in two laboratory-cultured strains of human cells.

The researchers found that when certain strains of E. coli bind to a molecule called CD55 on the surface of cells lining the interior of the intestine using a protein called afaE, it causes a sudden increase in production of an immune molecule called MICA.

The boosted MICA levels prompt "natural killer" (NK) immune cells to release gamma interferon. This protein triggers the production of immune cells called macrophages, which the researchers suspect could be linked to the chronic inflammation associated with this digestive disorder.

"We believe that it could be one of the parameters … which could increase and perpetuate the local inflammation in the bowel," says Toubert.

His team also examined samples of colon tissue surgically removed from 18 patients with Crohn's disease and compared them to normal colon tissue removed during colon cancer surgery. They found increased MICA production in the cells taken from patients with Crohn's disease, compared to the normal colon tissue samples.

He suspects other bacteria may have the same effect. "We have seen this effect with [diffusely adherent] E. coli, but it may be the case for other strains which we have not tested," he says.

Dr. R. Balfour Sartor, a professor of medicine, microbiology and immunology at the University of North Carolina at Chapel Hill, studies the relationship between bacteria and inflammatory bowel disease.

"They're establishing a possible mechanism by which a bacteria that adheres to the surface of an [intestinal lining] cell could then activate a response in NK cells," as well as certain classes of cells that mediate immunity, says Sartor.

He says the findings, while consistent with animal studies of a bacterial agent stimulating inflammation that could potentially lead to IBD, don't show that this type of inflammation occurs only in IBD.

However, he notes that studies have shown that a high percentage of IBD patients showing early reactivation of disease after surgery have a form of E.coli in their system.

Toubert stresses these findings are preliminary, but says it may indicate that antibiotic treatments in some patients with IBD would be beneficial.

According to Sartor, "it's clear that antibiotics do have a role in treating Crohn's patients, particularly those that have colonic involvement." The antibiotics Flagyl (metronidazole) and Cipro (ciprofloxacin) are most commonly used, he says, but he notes Flagyl doesn't affect E. coli, suggesting other bacterial agents are at work.

Toubert now plans to carry out more detailed studies of immune cells from inflammatory lesions in the intestinal lining of IBD patients.

What To Do

The National Institute of Diabetes & Digestive & Kidney Diseases provides this information on Crohn's disease, irritable bowel syndrome and ulcerative colitis.

You can also check out this information from the Crohn's & Colitis Foundation of America.

SOURCES: Interviews with Antoine Toubert, M.D., Ph.D., associate professor, Laboratory of Immology and Histocompatibility, University Institute of Hematology, Hôpital Saint-Louis, Paris; R. Balfour Sartor, M.D., professor, Division of Digestive Diseases and Nutrition, Department of Internal Medicine, University of North Carolina School of Medicine, Chapel Hill, N.C.; Feb. 5, 2002, Proceedings of the National Academy of Sciences
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