Bacterias Role in Bowel Cancer | The Scientist Magazine

20/03/14 14:33

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Bacterias Role in Bowel Cancer

The development of serrated polyps depends on bacteria present in the gut, a mouse study
shows.
By Ashley P. Taylor | March 3, 2014
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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 the mice are genetically engineered, via a
pair of transgenes, to overexpress the growth factor
HB-EGF. But genetics, the researchers found, are
Clostridium botulinum
WIKIMEDIA, CDC
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 on the microbiota present in that 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 in humans
(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 Scientist in 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.

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Since researchers determined that the bacterium Helicobacter pylori can cause some stomach cancers, a
growing body of evidence has suggested that certain bacteria influence cancer development.

4. Stem Cells Remember

Substrates

After finding that antibiotics prevented polyp formation, the researchers tried feeding the antibiotictreated 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.

5. A CRISPR Fore-Cas-t

The researchers also transplanted early embryos of the transgenic mice into females of another, cancerfree 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.

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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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Bacterias Role in Bowel Cancer | The Scientist Magazine

20/03/14 14:33

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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?

Avi Karn
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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.

GutMicrobes
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March 10, 2014

luchao
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aaaa
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