Research shows strong ties between gum disease and cancer

‘Troublemaking’ bacteria that is a major factor in periodontitis prevents the body from properly fending off cancerous cells, Hebrew U research shows

An illustration of a cancer cell. (photo credit: Cancer image)
An illustration of a cancer cell. (photo credit: Cancer image)

Failing to keep your teeth clean could lead to more than yellowing and bad breath, according to research by a Hebrew University team. A study of oral pathogen Fusobacterium nucleatum, commonly found in the mouth, indicates that it can actually impede the body’s immune system from fighting certain diseases – like cancer.

In a paper published in the latest issue of the research journal Immunity, co-authors Dr. Ofer Mandelboim and Dr. Gilad Bachrach discovered that the F. nucleatum germ could “collude” with colon cancer cells to inhibit an immune cell receptor called TIGIT – a natural body defense to the spread of cancer.

“Certain bacteria have previously been shown to fight cancer, so the surprising finding of this paper is that bacteria such as Fusobacterium nucleatum can grant tumors an anti-immune defense mechanism,” said Mandelboim of the Hebrew University Hadassah Medical School.

F. nucleatum has actually been implicated in a long list of trouble-making activities in the body. Once thought to be a harmless bacterium that got washed away with a good gargle, the bacteria – a major contributor to periodontitis, a disease of the gums – has been linked to heart disease, HIV and stillbirth.

The new study is the first one to establish a solid connection between F. nucleatum’s activities and a specific worsening in the condition of cancer patients.

F. nucleatum’s  record made it a likely candidate for a study on its interaction with cancer. Mandelboim teamed up with Bachrach of the Hebrew University-Hadassah School of Dental Medicine – a world expert on the F. nucleatum as a factor in periodontal disease – the two discovered that the bacterium was found not only in the mouth, but in human colorectal tumors as well.

There, a protein on the outer membrane of F. nucleatum, called Fap2, attaches itself to the TIGIT immune cell receptors – a component of the “natural killer cells” in the body’s nonspecific (innate) immune system that can prevent the spread of cancer. This “relationship” somehow prevents the TIGIT receptors from acting properly – compromising the activity of the killer cells, and allowing the cancer cells to grow and spread.

The findings may help researchers devise new ways of fighting cancer. If interaction between F. nucleatum and the TIGIT receptors prevents them from properly fighting cancer, then keeping those two elements apart could bolster the immune system, said Mandelboim. “Blocking the interaction between these bacteria and immune cells might improve anti-tumor immunity both in general and with regard to colon cancer in particular.”

How does F. nucleatum get from the mouth to the colon? Via the bloodstream, research shows. It’s the same way the germ gets from the mouth to the heart or to the uterus.

In one case cited by the US National Institutes of Health, for example, a woman with pregnancy-associated gingivitis (a common condition in pregnant women) experienced a respiratory infection, and gave birth to a stillborn. F. nucleatum, the NIH study said, appeared to be responsible, and “may have translocated from the mother’s mouth to the uterus when the immune system was weakened during the respiratory infection.”

Researchers at Case Western University in the US found the same method of transmission in interaction between F. nucleatum and HIV in patients.

The next step, said Chamutai Gur, a member of the research team, is to see if removing FAP2 or preventing it from binding with TIGIT changes the prognosis of patients.

“The implications are that if we either remove the Fusobacterium nucleatum bacteria from the tumors or inhibit TIGIT with antibodies, we might enable immune cells to kill the colon tumors more efficiently.”

So can keeping the teeth and mouth clean – for example, by brushing the teeth regularly – help prevent colon cancer? Not necessarily, say experts; colon cancer is tied to a number of factors, including age, weight, lifestyle and other environmental conditions.

But the research is clear: the less Fusobacterium nucleatum in the mouth, the less chance for it to penetrate the bloodstream and end up in the colon, facilitating the spread of cancer.

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