Researchers have found that a specific subtype of Fusobacterium nucleatum may be capable of growing within colorectal cancer, driving cancer progression, and leading to poorer outcomes following colorectal cancer treatment, according to a recent study published by Zepeda-Rivera et al in Nature. The findings could help improve therapeutic approaches and early screening methods for colorectal cancer.
Background
Colorectal cancer is the second leading cause of cancer mortality among adults in the United States. Fusobacterium nucleatum is commonly found in the mouth; however, the researchers suggested that the bacteria may be able to travel into the gut.
“We’ve consistently seen that patients with colorectal [cancer] tumors containing Fusobacterium nucleatum have poor survival and poorer prognoses compared with patients without the microbe,” emphasized co–senior study author Susan Bullman, PhD, a cancer microbiome researcher at Fred Hutchinson Cancer Center. “Now, we’re finding that a specific subtype of this microbe is responsible for tumor growth. It suggests therapeutics and screening that target this subgroup within the microbiota would help [patients] who are at a higher risk for more aggressive colorectal cancer,” she added.
Study Methods and Results
In the recent study, the researchers examined the levels of Fusobacterium nucleatum within the tumors removed from 200 patients with colorectal cancer—with the goal of determining how the microbe travels from its typical environment to a distant site in the lower gut and subsequently contributes to cancer progression.
The researchers discovered that a specific subtype of the Fusobacterium nucleatum, Fna C2, was elevated in the tumor tissue of about 50% of the patients. They also found that the microbe was present in higher numbers within the stool samples of patients with colorectal cancer compared with the stool samples of healthy individuals. Additionally, the predominant group of Fusobacterium nucleatum in the colorectal cancer, originally thought to be a single subspecies, was actually composed of two distinct clades.
“This discovery was similar to stumbling upon the Rosetta Stone in terms of genetics,” highlighted co–senior study author Christopher D. Johnston, PhD, a molecular microbiologist at Fred Hutchinson Cancer Center. “We have bacterial strains that are so phylogenetically close that we thought of them as the same thing, but now we see an enormous difference between their relative abundance in tumors vs the oral cavity,” he continued.
The researchers identified 195 genetic differences between the clades, and uncovered that the tumor-infiltrating Fna C2 subtype had acquired distinct genetic traits allowing it to leave the mouth, withstand stomach acid, and grow in the lower gastrointestinal tract. After comparing tumor tissue with healthy tissue from patients with colorectal cancer, the researchers noted that only the subtype Fna C2 was significantly enriched in colorectal cancer tissue and responsible for cancer progression.
Conclusions
The new findings may present novel opportunities for developing microbial cellular therapies using modified versions of bacterial strains to deliver treatments directly into the colorectal cancer.
“We have pinpointed the exact bacterial lineage that is associated with colorectal cancer, and that knowledge is critical for developing effective preventive and treatment methods,” Dr. Johnston underscored.
Disclosure: The research in this study was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health, the National Cancer Institute, the W.M. Keck Research Foundation, and a Washington Research Foundation Fellowship. For full disclosures of the study authors, visit nature.com.
