Study underway to evaluate role of biofilms like E. coli in colon cancer risk

Francis M. Giardiello

A clinical trial is underway to further examine the role of Escherichia coli and Bacteroides fragilis in the formation of colon cancer among patients with familial adenomatous polyposis, a hereditary form of the disease.

The research builds on prior investigations that showed E. coli and B. fragilis form a film on the colon before polyps appear.

The goal of the NIH-funded trial is to obtain a larger number of colonic biofilms from 2,000 adults with familial adenomatous polyposis (FAP) to confirm previously published trends.

Trial results could help determine whether those at risk for colon cancer could be identified with a simple stool test.

HemOnc Today spoke with Francis M. Giardiello, MD, professor of medicine in the department of oncology at Johns Hopkins University, about how this discovery came about; what key questions remain; and the potential implications the findings will have on screening, early detection and colon cancer outcomes.

Question: Can you provide a brief overview of how this discovery came about?

Answer: The key concept is the concept of the microbiome, specifically biofilms. The microbiome involves organisms that are in our body. There are trillions of these organisms in and on our body — more than we have human cells within the body.

In the colon, one can think of the microbiome in two ways. One way is the organisms flowing through the colon, and a second way is the organisms that stick to the side of the colon, which are known as biofilms. The concept of a biofilm goes back quite a long time. It first came to scientific notoriety in the 1930s, and then it was explored to some degree during the 1990s and 2000s. It was discovered that biofilms are found throughout the body. Classically, we find biofilms sticking to the tissues in the mouth, but researchers also found that these biofilms are sticking to the colon. However, they did not know what they were doing there. In 2014, Cynthia L. Sears, MD, discovered that people with colon cancer — specifically on the right side of the colon — had these biofilms present in the cancer and also on the right side of the colon. She came up with the association of right-sided colon cancer and presence of colorectal biofilms. She also did some great work in which she took mice that had a predilection to colon cancer and took some of the biofilms that were in humans who had colon cancer and gave them to the mice. The mice went on to develop tumors. She also ground up tissue from humans who did not have polyps and the mice did not go on to develop polyps. Putting this information together, we derived the hypothesis that these biofilms may be associated with the genesis of colon polyps and colon cancer.

Q: What key questions are you and colleagues aiming to answer now?

A: We started this grant-funded study a little more than a year ago. The key questions we are trying to answer are: How prevalent are these biofilms in humans? Are they associated with colon cancer or polyps? What are these biofilms made up of? What do they do to the colon mucosa?

Q: Can you provide more details about the study?

A: It is a 5-year study funded by NCI. We are recruiting patients as they undergo colonoscopy. We are collecting the patients’ stool and they are given a questionnaire about their demographics, lifestyle and diet. We then ask them for samples of saliva, urine and blood. They then undergo colonoscopy, and we perform biopsy to look for these biofilms.

Q: What could the potential implications of your findings be on screening, early detection and colon cancer outcomes?

A: It is pretty exciting. If our hypothesis is correct that these biofilms are associated with colon cancer and potentially are a precipitating or accelerating factor, then the implications can become quite wide. There is about a 15% rate of these biofilms in humans on colonoscopy. This correlates with patients who have polyps on screening, which is about 20%. The finding could be a marker for persons at high risk for colorectal cancer. It could be a causative factor with colorectal cancer and/or precancerous polyps and the implications would be important. One could check for this marker on colonoscopy and, if it is a causative factor, try to eliminate or change the microbiome of the colon to decrease the risk for colon cancer. So, the implications could be quite dramatic given that about 5% of patients have colon cancer and 20% of patients have adenomas that can go on to become colon cancer. – by Jennifer Southall

Reference:

Dejea CM, et al. Science. 2018;doi:10.1126/science.aah3648.

For more information:

Frances M. Giardiello, MD, can be reached at John Hopkins University, 3400 N. Charles St., Baltimore, MD 21218.

Disclosure: Giardiello reports no relevant financial disclosures.