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New ideas on how gut bacteria cause ulcers, cancer

By Alison McCook

Last Updated: 2003-05-29 15:53:18 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Research released Thursday may offer a new explanation for how a bacterium known to cause ulcers and stomach cancer does its damage in the gut.

Reporting in the journal Science, researchers in U.S. and Italy discovered that a form of the bacterium, known as Helicobacter pylori, may cause problems in the gut by disrupting the junctions between the cells that make up the protective stomach lining.

These junctions contain important substances that help the body with numerous processes, such as repairing damaged stomach cells, study author Dr. Manuel Amieva of Stanford University in California told Reuters Health.

Disrupting those junctions may prevent the body from repairing damage in the stomach when it occurs, perhaps allowing a relatively minor problem to eventually progress to something more serious, such as an ulcer or stomach cancer, Amieva said.

The research focused on the form of H. pylori that contains a gene known as CagA. Among different types of H. pylori, the CagA-carrying form is presumed to be particularly capable of causing illness, Amieva said. He estimated that slightly more than half of H. pylori strains may carry CagA.

During the study, Amieva and his team discovered that removing CagA prevents H. pylori from disrupting these junctions, suggesting that the CagA protein plays an important role in this process, he noted.

Based on these findings, it may one day be possible to protect people from CagA-carrying bacteria by designing a drug or vaccine that blocks CagA, the researcher said.

However, he cautioned that researchers need to learn more about how CagA causes damage in the body before they can begin designing therapies that stop it.

"I think we're just starting to get at the biology of what's going on," Amieva said. "I think we need to know more first about what (CagA) is doing."

"We don't know that CagA directly is causing the ulcers or causing the cancers ... there's probably other things that contribute to this," he added. "What we do know is that if you have CagA around, then you are more likely to get these diseases."

Approximately half of the population carries H. pylori, which usually causes no harm but, in some instances, can increase the risk of ulcers, gastritis, and stomach cancer.

Amieva explained that researchers have known that around 10 percent of all the bacteria found in the stomach attach to the cells that make up the stomach lining. Working with samples of stomach cells in the laboratory, Amieva and his colleagues discovered that once attached to those cells, only forms of H. pylori that carry CagA concentrate around the edges between two cells, near the junctions that hold stomach lining cells together.

"If we remove the CagA gene from the bacteria, they still attach to the cells, but they don't concentrate over the junction," Amieva said.

Once near the junctions, the bacteria inject the CagA protein into the lining cells. After that occurs, the researchers found that the proteins that make up the junctions begin to migrate away from the junctions and towards the H. pylori cells, thereby disrupting the integrity of the region.

And after removing the CagA gene from H. pylori, the researchers saw that the proteins involved in the junctions no longer migrated toward the attached bacteria, leaving the junctions intact.

Amieva added that a recent study suggests that H. pylori may also cause ulcers by secreting a protein that binds to the surface of stomach-lining cells and causes the lining to break apart, exposing the stomach to ulcer-causing substances such as acid and bile.

"It is possible that there are other insults that disrupt the (stomach lining) and start the process of forming an ulcer," he said.

Copyright 2002 Reuters.