A microscope image shows a human colorectal cancer tumor with Fusobacterium nucleatum stained in a red-purple color. Credit: Fred Hutchinson Cancer Center
Key points:
- Researchers have found a specific subtype of Fusobacterium nucleatum in colorectal cancer tumors.
- The tumor-infiltrating Fna C2 bacteria acquired distinct genetic traits that enable it to travel from the mouth through the stomach to grow in the lower gastrointestinal tract.
- The results of this study highlight the potential of developing therapies that use modified versions of bacterial strains to deliver treatment directly into tumors.
Researchers identified a specific microbe subtype that can travel from the mouth to the gut and grow within colorectal cancer tumors. Their findings, published in Nature, may help improve therapeutic approaches and early screening methods for colorectal cancer.
The research team examined colorectal cancer tumors removed from 200 patients and measured levels of Fusobacterium nucleatum—a bacterium known to infect tumors. This microbe’s typical environment is the mouth and researchers hoped to determine how it migrated to the lower gut and contributed to colorectal cancer growth.
Researcher’s first surprising finding was that the predominant group of Fusobacterium nucleatum in colorectal cancer tumors, thought to be a single subspecies, is actually composed of two distinct lineages known as “clades.”
“This discovery was similar to stumbling upon the Rosetta Stone in terms of genetics,” said study author Christopher Johnston of the 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 versus the cavity.”
The team separated out the genetic differences between the clades and found that the tumor-infiltrating Fna C2 type acquired 195 distinct genetic traits that enabled it to travel from the mouth through the stomach to grow in the lower gastrointestinal tract.
Comparing tumor tissue with healthy tissue from patients with colorectal cancer revealed that only subtype Fna C2 was significantly enriched in tumor tissue and supported colorectal cancer growth. Researchers found that this subtype of the bacterium was elevated in the tumor tissue in about 50% of cases.
The results of this study highlight opportunities for developing microbial cellular therapies that can use modified bacterial strains to deliver treatment directly into tumors.
“We have pinpointed the exact bacterial lineage that is associated with colorectal cancer, and that knowledge is critical for developing effective prevention and treatment methods,” said Johnston.