Common Oral Bacterium May Promote Growth of Colorectal Tumors

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A bacterium commonly found in the mouth appears to play a role in triggering the development of some colorectal tumors, according to the results of two recent studies published in the August issue of Cell Host & Microbe.

Earlier studies revealed that certain gut bacteria may accelerate growth of colitis-associated colorectal tumors, but it was not known whether the same was true for colorectal cancer not associated with inflammatory bowel disease.

Related: Bacterial Colitis Promotes Development of Colorectal Cancer

A research team led by Wendy Garrett, MD, of Harvard Medical School, Boston, MA, noted that various species of Fusobacterium, a commensal anaerobe linked to several types of periodontal disease, are enriched in colorectal tumors.1 The research team sought to determine whether the bacterium contributes to tumor development or if the association is indirect.

Study results showed that 48% of colonic adenomas from patients who had no history of inflammatory bowel disease harbored greater numbers of Fusobacterium species than the surrounding healthy tissue.1

In addition, more Fusobacterium species were found in fecal samples from patients with colorectal cancer or colonic adenomas when compared with samples from people who did not have either condition.

The researchers then fed a single species, Fusobacterium nucleatum, to mice bred to develop intestinal tumors and found that the bacterium accelerated the development of colonic tumors without inducing colitis. The tumors had high concentrations of myeloid cells, which trigger inflammation and promote tumorigenesis.

Examination of human colorectal cancer tumors found an immunological profile similar to that of the Fusobacterium-fed mice.

“Collectively, these data support that F. nucleatum modulates the tumor-immune microenvironment and results in the expansion of myeloid-derived immune cell types that have been reported to promote tumor progression,” the authors wrote. “In contrast to other bacterial-driven models of intestinal tumorigenesis, we have found a specific bacterial strain that accelerates intestinal tumorigenesis in the absence of colitis.”

A second research team led by Yipang Han, PhD, of Case Western Reserve University, Cleveland, OH set out to determine the mechanisms by which F. nucleatum promotes tumor growth.2

This team demonstrated that the key to the tumor-promoting effects of Fusobacterium nucleatum is its unique adhesin FadA, which binds to human colorectal cancer cells and allows the bacterium to invade them. FadA activates genes that promote cancer growth, triggers inflammation in the cancer cells, and facilitates formation of tumors.

FadA gene levels in colon tissue from patients with adenomas and adenocarcinomas were found to be 10 to 100 times higher than levels in tissue from healthy individuals.

In a statement Dr. Han said, “We showed that FadA is a marker than can be used for the early diagnosis of colorectal cancer and identified potential therapeutic targets to treat or prevent this common and debilitating disease.”

Based on the study outcomes, both research teams suggested that, if Fusobacterium species are shown to play an important role in tumorigenesis in human colorectal cancer, reduction of their population in the oral cavity or gastrointestinal tract might delay or prevent tumor progression in patients at high risk for colorectal cancer.



References

1. Kostic AD, Chun E, Robertson L, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe. 2013;14:207-215.

2. Rubinstein MR, Wang X, Liu W, et al. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating e-cadherin/b-catenin signaling via its FadA adhesion. Cell Host Microbe. 2013;14:195-206.

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