A strain of mouth bacteria that causes gum disease may have a more lethal health consequence: colorectal cancer. This is according to two independent studies — one from Harvard, the other from Case Western Reserve University — published today in the journal Cell Host & Microbe.

Colorectal cancer is the second most common form of cancer in the world, with rates being about 30 percent higher in developed countries. Nearly 50,000 people in the U.S. will die from colorectal cancer this year.

Prior work in mouse models has shown that gut bacteria, which include species found in the mouth, can promote the development of colon tumors.

Over the last two years, a series of genetic studies on human colon biopsies revealed that one family of microbes — Fusobacteria — is present in healthy tissue adjacent to colorectal cancer.

Although Fusobacteria start off in the mouth and are frequently associated with gum disease, they can migrate through blood vessels to far reaches of the intestinal tract, including the colon. However, none of these earlier investigations had observed the bacteria within the actual tumors.

This led investigators at Harvard to look at earlier stages of colon cancer to see if this discrepancy was merely an issue of timing. They found fresh evidence that Fusobacteria are intimately nestled within tumors of the colon.

"Fusobacteria may provide not only a new way to group or describe colon cancers but also, more importantly, a new perspective on how to target pathways to halt tumor growth and spread," said senior study author Dr. Wendy Garrett of the Harvard School of Public Health and the Dana-Farber Cancer Institute.

Garrett and her team discovered that Fusobacteria species are enriched in biopsy samples of colonic adenomas. These start off as benign tumors of intestinal lining, but can become malignant and are the leading precursor of colorectal cancer. The samples were pulled from patients across the U.S. and from University of Aberdeen School of Medicine in Scotland, suggesting this bacterial mouth-to-colon relationship is a global phenomenon.

Further supporting this connection, the team found that Fusobacteria elevate the generation of tumors in a mutant mouse strain that is prone to developing intestinal cancer. Infection with these microbes attracts a particular brand of immune cell — myeloid cells — which the authors found stimulates inflammatory responses that can cause cancer.

Fusobacteria’s Growing ‘Fad’

The second investigation examined how Fusobacteria are able to set up shop in the intestines. In 2011, a research team led by Dr. Yiping Han, a professor of periodontics at Case Western, found that Fusobacteria produce an adhesion molecule called “FadA” that allows the microbe to attach to blood vessels.

After a suspected link was made two years ago between that Fusobacteria and colon cancer, Han and her team switched their attention to tumors.

"This was one of those serendipitous scientific moments in making this discovery," Han said.

In their latest study, they found that FadA levels were between 10 and 100 times higher in patients with adenomas and adenocarcinomas, the cancerous cousin of the former.

In addition, her team designed a novel synthetic peptide that could block FadA and prevent Fusobacteria from invading cells growing in a Petri dish. They are now filing for a patent and believe this work will lead to possible treatments for colon cancer as well as oral disease.

"FadA can be used as a diagnostic marker for early detection of colon cancer,” concluded Han. “It can also be used to determine if treatment works effectively at reducing Fn load in the colon and the mouth."

Sources: Roxana Rubinstein MR, Wang X, Liu W, Hao Y, Cai G, Han YW. Fusobacterium nucleatum Promotes Colorectal Carcinogenesis by Modulating E-Cadherin/b-Catenin Signaling via its FadA Adhesin. Cell Host & Microbe. 2013.

Kostic AD, Chun E, Robertson L, et al. Fusobacterium nucleatum Potentiates Intestinal Tumorigenesis and Modulates the Tumor-Immune Microenvironment. Cell Host & Microbe. 2013.