Two research teams have published studies in Cell Host & Microbe that discuss how gut microbes known as fusobacteria, which are found in the mouth, stimulate bad immune responses and turn on cancer growth genes to generate colorectal tumors. The findings could lead to more effective strategies for the early diagnosis, prevention, and treatment of colorectal cancer, say the scientists.
“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,” says senior study author Wendy Garrett, Ph.D., of the Harvard School of Public Health and the Dana-Farber Cancer Institute.
Colorectal cancer is the second leading cause of cancer-related death in the United States. Recent studies have shown that fusobacteria from the mouth are also abundant in tissues from colorectal cancer patients. But until now, it was not known whether these microbes directly contribute to the formation of tumors.
In one of the new studies, Garrett, Matthew Meyerson, M.D., Ph.D., from Dana-Farber, and colleagues found that fusobacteria are prevalent in human adenomas, which are benign tumors that can become malignant over time, suggesting that these microbes contribute to early stages of tumor formation. In a mouse model of colorectal cancer, these bacteria accelerated the formation of tumors by attracting myeloid cells, which invade tumors and stimulate inflammatory responses that can cause cancer.
In the second study, Yiping Han, Ph.D., of Case Western Reserve University School of Dental Medicine, and her collaborators discovered that fusobacteria rely on Fusobacterium adhesin A (FadA), which is found on the surface of these bacterial cells, to attach to and invade human colorectal cancer cells. FadA then turns on cancer growth genes and stimulates inflammatory responses in these cells and promotes tumor formation.
Dr. Han and her team also found that FadA levels were much higher in tissues from patients with adenomas and colorectal cancer compared with healthy individuals. Moreover, they identified a compound that can prevent FadA’s effects on cancer cells.
“We showed that FadA is a marker that can be used for the early diagnosis of colorectal cancer and identified potential therapeutic targets to treat or prevent this common and debilitating disease,” explains Dr. Han.