Gut bacteria may cause cancer by disarming immune system

Date: Sep-03-2013New research presented at a conference this week suggests a common stomach bacterium with known links to duodenal ulcers and stomach cancer may trigger disease by disarming a part of the immune system that is
involved in controlling inflammation.

Strong evidence from epidemiological research - studies that look at incidence of disease and possible causes in
populations - and evidence from molecular studies has led to the idea that bacteria can cause
cancer.

One of these pathogens is Helicobacter pylori, a bacterium that establishes a life-long infection in humans
and is estimated to inhabit the stomach lining of around half the world's population.

At the Society for General Microbiology Autumn Conference 2013, which is taking place this week, researchers from
the University of Nottingham in the UK presented findings that they hope will give us a clearer understanding of how
H. pylori interferes with the human immune system so it can thrive in the mucosal lining of the stomach.

Katie Cook, from Nottingham's Faculty of Medicine & Health Sciences, presented the work and says:

"To identify people who are likely to suffer from stomach cancer, we need to understand how H. pylori
interacts with the cells of the stomach lining."

Cook and colleagues found that H. pylori is able to suppress the body's natural production of human beta
defensin 1 (hβD1), an antimicrobial agent found in the stomach lining, where it helps to stave off bacterial
infection.

They made their discovery by examining tissue samples biopsied from the stomach lining of 54 patients being treated
at Nottingham's Queens Medical Centre.

The team found that levels of hβD1 were ten times lower in patients infected with H. pylori, and patients with the
lowest level of the antimicrobial agent had the highest level of the bacteria.
Bacteria colonies damage tissue

Previous studies have already discovered how the more damaging strains of H. pylori manage to infect cells:
they construct a "molecular syringe" and use it to squirt bacterial products into the cells.

For their study, the team examined this mechanism in cultures of human stomach lining cells and found that the
syringe method, which is called cagT4SS, activates pathways that suppress production of hβD1.

These pathways are already known to be involved in triggering inflammatory responses. So by deactivating that part
of the immune system, the more damaging H. pylori strains help themselves to survive and set up colonies, and
gradually, over decades, damage the tissue they invade.

This mechanism could explain why chronic inflammation of the stomach lining is so strongly linked to cancer of the
stomach.

According to the American Cancer Society, more than half of all cases of stomach cancer are thought to be linked to
H. pylori infection.

Although 50% of people are infected with H. pylori, only 1-2% of them go on to develop gastric cancer.
However, survival rates are low because the symptoms do not usually emerge until the cancer is well-developed, and
diagnosis is often too late for a good prognosis.

On a more positive note, there is also evidence that people with H. pylori have a lower risk of other types
of cancer, although the reason for this is somewhat of a mystery. There is even evidence that H. pylori may protect against stroke.

Cook says:

"We hope to combine this work with that being carried out by our colleagues in order to develop a diagnostic test to
predict the future risk of gastric cancer development."

Written by Catharine Paddock PhD

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