How Diarrhoeal Bacteria may Cause Some Colon Cancers

Johns Hopkins scientists have gained significant insights into how bacteria that cause diarrhoea may also be responsible for some colon cancers.

The researchers have found that strains of the common Bacteroides fragilis (ETBF) dupe immune system cells into permitting runaway colon tissue inflammation, a precursor for malignant growth.

"This could be the H. pylori of colon cancer," Nature magazine quoted Dr. Cynthia Sears, Johns Hopkins infectious disease specialist, as saying, referring to the bacteria long known to cause stomach ulcers and suspected of causing the majority of stomach cancers.

During the study, she and her colleagues observed that ETBF uses tissue inflammation to cause colon cancer in a similar way that H. pylori causes stomach tumours.

In their study report, the researchers have highlighted the fact that a so-called enterotoxigenic bacterium is widely known to cause diarrhoea in children and adults, and that a previous study in Turkey has linked it to colon cancer.

While the bacteria does not cause any symptoms in some individuals, others develop diarrhoea 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 say.

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With a view to finding the link between ETBF and colon cancer, the researchers conducted a series of tests in mice bred to carry mutations in a colon cancer-causing gene called APC.

They observed that mice infected with ETBF developed diarrhoea that resolved quickly, but within a week, the animals developed inflammation and small tumours in the colon.

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One month later, the colons were pockmarked with tumours.

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

While evaluating the bacteria's effect on immune responses that may contribute to cancer development, the researchers observed that in ETBF-infected mice, there were high levels of a protein called pStat3, which, in its normal role, acts as a signal to trigger inflammation.

One of those signals activates an immune cell called T-helper 17 (Th17). Th17 cells produce molecules that have been implicated in fostering inflammation of tissues.

The researchers said that Th17 activity in the gut of germ-bearing mice was 100 times greater than normal, and when it was blocked, inflammation and tumour growth in the animals was reversed.

Dr. Drew Pardoll, an immunologist and cancer researcher at Johns Hopkins, speculates that in humans, infection with ETBF "produces a low-level inflammation that persists for a long time."

"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," Pardoll says.

Sears and Pardoll believe that ETBF may collude with other types of normal bacteria in the gut to promote cancer.

Given that the microbe itself is difficult to culture from stool specimens, th eresearchers 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.

The study has been published in the journal Nature Medicine.

Source-ANI
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