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Gut bacteria and bowel cancer

Monday 22 September 2008

“How gut bugs could trigger cancer” is the headline of the BBC News article. It reports that scientists have uncovered a chain reaction that could link ‘Enterococcus faecalis’, a type of bacterium that lives in our intestines, to the development of colon cancer. It continues that the bug is harmless in the vast majority of people, but that US scientists had found it could produce harmful chemicals, which can damage DNA. It quoted a UK expert as saying it was plausible that “bacteria could cause colon cancer” and that it is very unlikely that E. faecalis is the only bacterium that has such an effect.

The science behind this story is very preliminary and should not cause undue alarm. Any chain reaction underlying colon cancer is likely to be complex, as illustrated by the 42 interrelated genes assessed in this study. As mentioned by BBC News, E. faecalis is only one of many bacteria that inhabit the gut, many of which the body needs to function and, in most cases, are harmless.

Where did the story come from?

Dr Toby D. Allen and colleagues from the Muchmore Laboratories for Infectious Disease Research and other institutions in Oklahoma City, US carried out the research. The study was supported by a grant from the Office of Research and Development, the Medical Research Service, the Department of Veterans Affairs Medical Center and the Frances Duffy Endowment. The study was published in the peer-reviewed medical journal: Journal of Medical Microbiology.

What kind of scientific study was this?

For several decades, it has been suggested that bacteria in the gut play a role in the development of colorectal cancer. In this laboratory experiment, the researchers investigated the effect of the bacteria E. faecalis on live mice, in computer simulations and in studies of tissue from the large bowels of mice.

There were several different parts to this experiment. In one part, the researchers observed how colon cells reacted when they were exposed to bacteria in its “fermentation” state. This was done by growing the bacteria in the absence of the protein haematin. In this state, a kind of oxygen molecule called "superoxide" is produced, and it is this that is thought to damage DNA in surrounding cells.

The researchers wanted to compare the effects of E. faecalis bacteria that had been starved of haematin with E. faecalis that had been grown in its presence. (They refer to its ability to metabolise in this way as “dichotomous [dual] metabolism.”) To do this, they introduced the bacteria, or a control solution (without bacteria) into specially treated sections of the colon in mice, and assessed the effect of these different treatments on the appearance of the colon under the microscope after one to six hours.

They also looked at which genes were switched on and off in the colon during these treatments, and used computer modelling to look at how these genes were likely to interact. Immunohistochemistry, immunofluorescence and other more specialised tests and assays (examinations) were also conducted in order to build up a picture of how the bacteria affected the bowel.

What were the results of the study?

The researchers found no difference under the microscope in the structural appearance of the mouse colon after one to six hour’s treatment with E. faecalis. However, they found that the superoxide produced by the haematin-starved bacteria led to strong activation of a specific signalling pathway in immune cells called macrophages. This gave the researchers an idea of how the bacteria might be having their effect.

Mouse colons that were treated with the haematin-starved bacteria had altered productivity levels in certain genes associated with a number of processes including normal cell division and apoptosis (a type of cell death). Some of these genes have been implicated in certain forms of cancer. In total, the presence of E. faecalis in this state altered the expression of 42 genes linked to vital processes in human cells. The haematin-starved bacteria also stopped some cells grown in the laboratory from growing and dividing at a specific point in their life cycle.

What interpretations did the researchers draw from these results?

The BBC quotes one researcher as saying, "this research puts into perspective the complexity of the effects normal gut bacteria can have on the health of the individual." They conclude that the results demonstrate the uniquely dichotomous (dual) metabolism of E. faecalis, which can significantly modulate gene expression in the colonic mucosa for pathways associated with inflammation, apoptosis and cell-cycle regulation.

What does the NHS Knowledge Service make of this study?

This is an extensive set of microbiological studies that require a full interpretation to be made by experts in the field. Some who were asked to comment by the BBC have said that the bug is a candidate for cancerous changes, but that there is unlikely to be only one culprit that causes colon cancer. There are also many other factors which are involved, such as an individual’s genetics and environment. Some commentators point out that most people have these bacteria in their gut, but most people do not get colon cancer, “so there must be other factors involved.”

This study will help in the search for understanding which bacteria might be important and how they act. However, for now, this should be seen as a research interest.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

How gut bugs could trigger cancer.

BBC News, 22 September 2008

Links to the science

Allen TD, Moore DR, Wang X, et al.

Dichotomous metabolism of Enterococcus faecalis induced by haematin starvation modulates colonic gene expression.

Med Microbiol 57; 2008: 1193-1204