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Clostridium botulinumWIKIMEDIA, CDC

Bacterias Role in Bowel CancerThe development of serrated polyps depends on bacteria present in the gut, a mouse study

shows.

By Ashley P. Taylor | March 3, 2014

Changes to the microbial composition of the gut can

drastically alter the development of certain bowel

tumors, according to a study published today

(March 3) in The Journal of Experimental Medicine.

Researchers from New York Citys Icahn School of

Medicine at Mount Sinai worked with a mouse

model that develops tumors called serrated polyps

in the cecum, the part of the large intestine

proximal to the colon. The polyps arise in part

because themice are genetically engineered, via a

pair of transgenes, to overexpress the growth factor

HB-EGF.But genetics, the researchers found, are

not the whole story. Their work revealed that

bacteria are also required for tumor development

the ceca of transgenic mice raised on an antibiotic cocktail did not form polyps.

We were able to show that tumor formation was dependent onthe microbiota present inthat particular

area of the intestine, said Sergio Lira, who led the study. In the presence of antibiotics, or of a slightly

different cecum microbiota, the tumors did not develop.

This study adds to our knowledge of links between the gut microbiome and colon cancer, where

causation is now established in several animal models and correlations are intriguing inhumans

(although causation in humans are not yet proven), Rob Knight, a microbial ecologist at the University of

Colorado, Boulder, who was not involved in the work, told The Scientistin an e-mail.

Theres a growing body of information that constituents in the microbiota play a role in chronic

inflammation and in cancer development,said Martin Blaser, a professor of internal medicine and

microbiology at the New York University School of Medicine, who did not participate in the study. This

study supplies yet another model of the same phenomenon.

Since researchers determined that the bacterium Helicobacter pylorican cause some stomach cancers, a

growing body of evidence has suggested that certain bacteria influence cancer development.

After finding that antibiotics prevented polyp formation, the researchers tried feeding the antibiotic-

treated mice stool from their untreated counterparts to determine if bacteria alone could reverse the

effects of the drugs. After ingesting the gut bacteria from the untreated mice, the once germ-free mice

developed polyps.

The researchers also transplanted early embryos of the transgenic mice into females of another, cancer-

free mouse strain, Swiss Webster. Inoculated at birth with the bacteria of their surrogate mothers, these

transplanted mice did not develop tumors until 25 weeks, whereas the genetically identical controls had

tumors by 12 weeks. This showed that small changes in the gut microbiota could have a large influence

on tumor growth.

This essentially suggests that if you have a genetic mutation, Lira said, the same genetic mutation in

different individuals may have a different outcome.

When the researchers examined the animals bowels, they found both that bacteria had invaded the

intestinal epithelium and that the connections between the epithelial cellsas indicated by the presence

of cell adhesion molecules, including E-cadherinwere weakened where the polyps had formed,

compared with adjacent tissue. Most of the tumor-dwelling bacteria belonged to the Clostridiales family,

Lira said. The researchers also observed an upregulation of inflammatory molecules near the polyps.

One outstanding question, Lira said, is how microbes affect the intestinal epithelium: Do the bacteria

make it more permeable or just capitalize on its pre-existing weak spots?

We need now to go back and do longitudinal experiments throughout the development of the tumors to

try to understand what is causing the permeability changes that we have observed, he said.

G. Bongers et al., Interplay of host microbiota, genetic perturbations, and inflammation

promotes local development of intestinal neoplasms in mice, The Journal of Experimental

Medicine, doi: 10.1084/jem.20131587, 2014.

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Comments

March 3, 2014

Question: is it possible that these bacteria could be like bacteriophages

that host HPV-like viruses leading to chromosomal abnormalities and

possibly, cancer consecutively?

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March 3, 2014

This quote by Blaser says it all: This study supplies yet another model of

the same phenomenon. This is old news.

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March 10, 2014

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