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Research: ETBF may cause diarrhea in cancer patients

8/31/2009

BALTIMORE Johns Hopkins scientists say they have figured out how bacteria that cause diarrhea also may be the culprit in some colon cancers. The investigators say that strains of the common Bacteroides fragilis dupe immune system cells into permitting runaway colon tissue inflammation, a precursor for malignant growth.

“This could be the H. pylori of colon cancer,” stated Johns Hopkins infectious disease specialist, Cynthia Sears, referring to the bacteria long known to cause stomach ulcers and suspected of causing the majority of stomach cancers. Her studies suggest that ETBF uses tissue inflammation to cause colon cancer in a similar way that H. pylori causes stomach tumors.

A so-called enterotoxigenic bacterium, the germ is widely known to cause diarrhea in children and adults in the developing and developed world, and a previous study in Turkey has linked it to colon cancer.

The bacteria, which colonize in the gut, cause no symptoms in some individuals, but others develop diarrhea and colon inflammation, which has been linked to cancer growth. Unlike the case with H. pylori, it is unknown whether standard antibiotics can eradicate the microbe, experts said.

To track the link between ETBF and colon cancer, the Johns Hopkins researchers conducted a series of tests in mice bred to carry mutations in a colon cancer-causing gene called APC.

Their results, published in the Aug. 23 issue of Nature Medicine, show that mice infected with ETBF developed diarrhea which resolved quickly, but within a week, developed inflammation and small tumors in the colon. One month later, the colons were pockmarked with tumors.

Mice infected with a non-toxin producing strain of the bacteria were free of diarrhea, inflammation and tumors.

“If what we are seeing in mice holds true in humans, the chronic inflammation damages genetic material in the colon cells, allowing them to grow uncontrollably and develop into tumors earlier and more progressively than if they were not infected with ETBF,” commented Drew Pardoll, an immunologist and cancer researcher at Johns Hopkins.

Sears and Pardoll believe that ETBF may collude with other types of normal bacteria in the gut to promote cancer. The microbe itself is difficult to culture from stool specimens, according to the investigators, so they are working on blood tests to detect antibodies to the pathogen’s toxin, which may show whether an individual has been exposed to it and perhaps determine who may be at risk for colon cancer.

The investigators also envision vaccines and drug therapies that neutralize the pathogen’s toxin and its ability to inflame tissues.

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