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How Diarrheal Bacteria Cause Some Colon Cancers Revealed In Mouse Studies
ScienceDaily (Aug. 23, 2009) — Johns Hopkins scientists say they have figured out how bacteria that cause diarrhea may also be the culprit in some colon cancers. The investigators say that strains of the common Bacteroides fragilis (ETBF) dupe immune system cells into permitting runaway colon tissue inflammation, a precursor for malignant growth.
See also:
Health & Medicine
* Colon Cancer
* Colitis
* Gastrointestinal Problems
Plants & Animals
* Mice
* Bacteria
* Microbiology
Reference
* Metastasis
* Diarrhea
* Tumor
* Peptic ulcer
"This could be the H. pylori of colon cancer," says Johns Hopkins infectious disease specialist, Cynthia Sears, M.D., 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 say.
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 August 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.
Next, Sears and the Johns Hopkins team evaluated the bacteria's effect on immune responses that may contribute to cancer development.
In ETBF-infected mice, they found 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.
Th17 activity in the gut of germ-bearing mice was 100 times greater than normal, according to the investigators, and when they blocked the effects of Th17, they were able to reverse inflammation and tumor growth.
Drew Pardoll, M.D., Ph.D., 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 first witnessed the impact of diarrheal pathogens two decades ago in a refugee camp in Thailand where children, especially, were vulnerable to infection where water sanitation is poor. Most diarrheal disease is short-lived but can be very severe, Sears says, and it is common worldwide. The ETBF microbe is found in the gut of up to 20 to 35 percent of children and adults and, according to the Turkish study, in as many as 40 percent of colon cancer patients.
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.
Provisional patents for this technology have been filed.
Funding for the study was provided by the Crohn's and Colitis Foundation, the National Institutes of Health, Bernard Schwartz, William and Betty Topercer, Dorothy Needle, Bud Swartz, and the Commonwealth Foundation.
In addition to Pardoll and Sears, research participants include Shaoguang Wu, Ki-Jong Rhee, Emilia Albesiano, Shervin Rabizadeh, Xinqun Wu, Hung-Rong Yen, David Huso, Frederick Brancati, Elizabeth Wick, Florencia McAllister, and Franck Housseau at Johns Hopkins.
Adapted from materials provided by Johns Hopkins Medical Institutions, via EurekAlert!, a service of AAAS.
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These are tumors in the colons of multiple intestinal neoplasia (Min) mice colonized with enterotoxigenic Bacteroides fragilis (ETBF) for 3 months compared to Min mice not colonized with ETBF. The colons are stained with methylene blue. (Credit: Courtesy of Dr. Shaoguang Wu)
Related Stories
Cancer-causing Gut Bacteria Exposed (Sep. 22, 2008) — Normal gut bacteria are thought to be involved in colon cancer but the exact mechanisms have remained unknown. Now, scientists have discovered that a molecule produced by a common gut bacterium ... > read more
Inflammation Contributes to Colon Cancer (Jan. 15, 2009) — Researchers found that mice that lack the immune inhibitory molecule Smad3 are acutely sensitive to both bacterially-induced inflammation and ... > read more
Inflammation Contributes To Colon Cancer (Jan. 23, 2009) — Mice that lack the immune inhibitory molecule Smad3 are acutely sensitive to both bacterially-induced inflammation and ... > read more
Fruits And Veggies Not Likely Linked To Colon Cancer Risk (Sep. 28, 2007) — Eating fruits and vegetables was not strongly associated with decreased colon cancer risk, according to a new study. Several studies have examined the relationship between colon cancer and fruit and ... > read more
Better Treatments For Inherited Form Of Colon Cancer? (Nov. 10, 2008) — Researchers believe they may be one step closer to understanding how certain forms of colon cancer ... > read more
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How Diarrheal Bacteria Cause Some Colon Cancers Revealed In Mouse Studies
ScienceDaily (Aug. 23, 2009) — Johns Hopkins scientists say they have figured out how bacteria that cause diarrhea may also be the culprit in some colon cancers. The investigators say that strains of the common Bacteroides fragilis (ETBF) dupe immune system cells into permitting runaway colon tissue inflammation, a precursor for malignant growth.
See also:
Health & Medicine
* Colon Cancer
* Colitis
* Gastrointestinal Problems
Plants & Animals
* Mice
* Bacteria
* Microbiology
Reference
* Metastasis
* Diarrhea
* Tumor
* Peptic ulcer
"This could be the H. pylori of colon cancer," says Johns Hopkins infectious disease specialist, Cynthia Sears, M.D., 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 say.
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 August 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.
Next, Sears and the Johns Hopkins team evaluated the bacteria's effect on immune responses that may contribute to cancer development.
In ETBF-infected mice, they found 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.
Th17 activity in the gut of germ-bearing mice was 100 times greater than normal, according to the investigators, and when they blocked the effects of Th17, they were able to reverse inflammation and tumor growth.
Drew Pardoll, M.D., Ph.D., 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 first witnessed the impact of diarrheal pathogens two decades ago in a refugee camp in Thailand where children, especially, were vulnerable to infection where water sanitation is poor. Most diarrheal disease is short-lived but can be very severe, Sears says, and it is common worldwide. The ETBF microbe is found in the gut of up to 20 to 35 percent of children and adults and, according to the Turkish study, in as many as 40 percent of colon cancer patients.
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.
Provisional patents for this technology have been filed.
Funding for the study was provided by the Crohn's and Colitis Foundation, the National Institutes of Health, Bernard Schwartz, William and Betty Topercer, Dorothy Needle, Bud Swartz, and the Commonwealth Foundation.
In addition to Pardoll and Sears, research participants include Shaoguang Wu, Ki-Jong Rhee, Emilia Albesiano, Shervin Rabizadeh, Xinqun Wu, Hung-Rong Yen, David Huso, Frederick Brancati, Elizabeth Wick, Florencia McAllister, and Franck Housseau at Johns Hopkins.
Adapted from materials provided by Johns Hopkins Medical Institutions, via EurekAlert!, a service of AAAS.
Email or share this story:
| More
Need to cite this story in your essay, paper, or report? Use one of the following formats:
APA
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enlarge
These are tumors in the colons of multiple intestinal neoplasia (Min) mice colonized with enterotoxigenic Bacteroides fragilis (ETBF) for 3 months compared to Min mice not colonized with ETBF. The colons are stained with methylene blue. (Credit: Courtesy of Dr. Shaoguang Wu)
Related Stories
Cancer-causing Gut Bacteria Exposed (Sep. 22, 2008) — Normal gut bacteria are thought to be involved in colon cancer but the exact mechanisms have remained unknown. Now, scientists have discovered that a molecule produced by a common gut bacterium ... > read more
Inflammation Contributes to Colon Cancer (Jan. 15, 2009) — Researchers found that mice that lack the immune inhibitory molecule Smad3 are acutely sensitive to both bacterially-induced inflammation and ... > read more
Inflammation Contributes To Colon Cancer (Jan. 23, 2009) — Mice that lack the immune inhibitory molecule Smad3 are acutely sensitive to both bacterially-induced inflammation and ... > read more
Fruits And Veggies Not Likely Linked To Colon Cancer Risk (Sep. 28, 2007) — Eating fruits and vegetables was not strongly associated with decreased colon cancer risk, according to a new study. Several studies have examined the relationship between colon cancer and fruit and ... > read more
Better Treatments For Inherited Form Of Colon Cancer? (Nov. 10, 2008) — Researchers believe they may be one step closer to understanding how certain forms of colon cancer ... > read more
Search ScienceDaily
Number of stories in archives: 44,032
Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily's archives for related news topics,
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Just In:
Lightning's Mirror Image ... Only Much Bigger
Using Light To Teach Magnets New Tricks
Microchip Does 1,000 Chemical Reactions At Once
Naming Evolution's Winners And Losers
Inner 'Fingerprint' For Personal Medical Care
Why Sleep? To Boost Efficiency, Minimize Risk
Ultrathin LEDs: New Class Of Displays
Oxycholesterol: Greatest Heart Disease Risk?
Science Video News
Shedding Light On Colon Cancer
Biomedical engineers have developed a new technique to detect colon cancer. A thin optical fiber shines light onto the interior of the colon.. ... > full story
* Gastroenterologists Use Hi-Res Narrow-Band Imaging to Find Cancer
* Molecular Biologists Devise Strategy To Starve Brain Tumors
* Microbiologists Invent Coating To Protect Athletes From Infection
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* Encyclopedia of Life grows; clues on ageing, pests
* Satellites put into orbit for Japan and Australia
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* Gene swap experiment makes altering bugs easier
* more science news
In Other News ...
* Suspect in U.S. model murder found dead in Canada
* Netanyahu sees talks with Palestinians in 2 months
* Storm Bill loses steam in North Atlantic
* Fires near Athens recede after 3-day inferno
* Malaysian state to cane woman after Ramadan
* Justice Dept advises pursuing CIA abuses: report
* Facebook to boost staff by 50% in 2009: report
* U.S. presses sanctions to end N.Korea atomic plans
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