Science Editor

Terming it a possible "Helicobacter pylori of colon cancer," a team of American and Taiwanese scientists reported that they have identified a gut bacterial strain that causes colon cancer in mice.

So-called commensal bacteria, which colonize humans on both the outside and inside of their body, are increasingly recognized as not merely benign hangers-on, but in many ways, as almost a "forgotten organ" of the body. One recent study proposed that mammals essentially have outsourced some of their immunological functions to their gut bacteria over the course of evolution, coming to "depend on critical interactions with their microbiome . . . for health." (See BioWorld Today, May 29, 2008.)

But if some commensals pull their weight, others, apparently, befoul their nest.

The best-known example is indeed H. pylori, the stomach bacterium implicated in ulcers and, in extreme cases, gastric cancer. In their paper, which appeared in the Aug. 23, 2009, online edition of Nature Medicine, Franck Housseau, senior author Cynthia Sears and their colleagues at Johns Hopkins University and the Taiwanese Chang Gung University and Center for Traditional Chinese Medicine added enterotoxic Bacteroides fragilis, or ETBF, to the list of bad commensals.

Actually, ETBF bacteria were not exactly on the commensal A-list even before the newest study. They cause diarrhea through their secretion of the BFT toxin, and one previous study already had shown that they are more frequent in colon cancer patients than in the general population.

The new paper showed a possible reason why. The authors infected mice with either ETBF or NTBF, a related strain that does not produce enterotoxin. ETBF mice first developed a few days of diarrhea. One month later, their colons were thicker, inflamed and littered with tumors. Control mice developed neither the diarrhea nor the colonic tumors.

The ETBF bacteria activated the transcription factor Stat3, which "strongly skewed" the development of T cells toward TH17 cells, which secretes the proinflammatory interleukin-17 and is already a hot target in autoimmune disease circles. (See BioWorld Today, Jan. 7, 2008, and April 16, 2009.)

Th17 activity in the gut of ETBF-infected mice was increased by two orders of magnitude compared to controls, and blocking the IL-17 receptor prevented the carcinogenic effects of ETBF.

Co-corresponding author Cynthia Sears told BioWorld Today that in order to move the research forward toward the clinic, the first order of business would be to develop a "sensitive and specific diagnostic" for ETBF to see whether the findings hold up in humans. Her team currently is working on such a diagnostic.

If it is the case that people with colon cancer are more likely to be colonized with ETBF, there are three possible avenues: treating the bug, vaccinating against it or blocking the immune system response to it.

Scientifically, it is interesting that ETBF appears to do its damage via activating T cells.

The classical view of cancer and immunity is that innate immunity, which causes inflammation, may promote the development of tumors, while T cells are seen as potential anticancer weapons.

But with the discovery of TH17 helper T cells, that can themselves cause inflammation, that view is becoming more complex. "TH17, which secretes interleukin-17, has been widely involved now in chronic inflammation that has a procarcinogenic effect," co-corresponding author Franck Housseau explained.

It is a specific way in which the ETBF bacteria are similar to H. pylori: Both stimulate TH17 cells.