Study Reveals Connection Between Foodborne Toxin and Spread of Colorectal Cancer
A recent study has uncovered a significant link between a toxin produced by the common foodborne bacterium Campylobacter jejuni (C. jejuni) and the metastasis of colorectal cancer. Conducted by researchers at the University of Florida Health Cancer Center in collaboration with international experts, the findings were published in the journal Cell Host & Microbe.
The research indicates that the cytolethal distending toxin (CDT), produced by certain strains of C. jejuni, plays a crucial role in accelerating the spread of colorectal tumors to distant organs. This discovery holds potential for developing new methods for early detection of metastatic colorectal cancer, which could improve treatment strategies for affected patients.
According to Dr. Christian Jobin, a prominent figure in the study and a distinguished professor at the UF College of Medicine, this research enhances the understanding of how bacterial toxins influence the progression of colorectal cancer. The study began with former postdoctoral researcher Zhen He in Jobin's laboratory.
The gut microbiota, which is comprised of various microorganisms, is known to affect numerous health aspects, including digestion and immune regulation. Additionally, the microbiota influences the progression of several cancers, including colorectal cancer, which is the second leading cause of cancer-related deaths in the United States.
C. jejuni is responsible for over two million cases of foodborne illness annually in the U.S. Some strains of this bacterium produce the toxin CDT, which previous research by Jobin's team showed to be critical in inducing colorectal cancer in murine models.
In the current study, the research team aimed to explore how C. jejuni influences cancer metastasis. Early detection of colorectal cancer is vital, as patients diagnosed before metastasis have a five-year survival rate of approximately 90%. Conversely, metastases are the leading cause of cancer mortality, and treatment options for those affected are often limited.
To investigate, the researchers compared tissue samples from 34 patients with primary colorectal cancer who developed metastasis with samples from 37 patients who did not experience metastasis over a three-year follow-up period. The results revealed a notable presence of C. jejuni in the metastatic patients, indicating that those with detectable bacteria had a significantly worse prognosis than those without.
These findings were corroborated with data from extensive national tumor sample databases. Dr. Jobin stated that the presence of CDT is integral to the bacteria's role in facilitating cancer spread, noting that when CDT-producing bacteria invade tumors beyond the gastrointestinal tract, they seem to enhance the tumors' aggressiveness.
Utilizing laboratory mice with metastatic lung and liver tumors, alongside human colorectal cancer tissue and three-dimensional tumor models derived from patient cells, the researchers demonstrated how CDT contributes to cancer spread. The study revealed that CDT increases the expression of several enzymes and activates signaling pathways in cancer cells associated with metastasis.
Several clinical trials are currently underway to test drugs that target these signaling pathways, and the insights from this study may help direct the development of new therapeutic options for colorectal cancer patients.
Additionally, the team successfully isolated live C. jejuni from tumors located outside the gastrointestinal tract, suggesting that the tumor environment may support bacterial growth. Further research is necessary to unravel the mechanisms by which the bacteria migrate to tumor sites and how the toxin activates specific cellular signaling pathways.
In summary, this pivotal research sheds light on the interplay between foodborne pathogens and cancer progression, creating opportunities for enhanced screening and targeted treatment for colorectal cancer patients.
