According to the American Cancer Society, “colorectal cancer is the third most common cancer diagnosed in both men and women in the United States, excluding skin cancers” and is responsible for over 50,000 deaths annually.
In a recent newspaper article published in New York Times, “Gut Microbes Combine to Cause Colon Cancer, Study Suggests” by Gina Kolata, researchers have found a potential link of toxin-producing Bacteroides fragilis and Escherichia coli strains to the exacerbation of colonic tumors in patients with familial adenomatous polyposis (FAP). The genes for these oncotoxins, specifically colibactin and Bacteroides fragilis toxin, were found to be expressed in FAP patient colonic mucosa at a higher frequency than those of patients without FAP.
These bacteria work together to form their own habitat (biofilm) within the intestinal barrier, where they flourish and cause chronic inflammation, DNA damage, and the possibility of subsequent tumors. It was also shown that, in subjects colonized with only one bacterial strain or the other, tumor onset was not as rapid as when colonized with both bacterial strains.
Subjects colonized with both bacterial strains also suffered increased mortality when compared to subjects colonized with only one strain or the other.
Colibactin is a bacterial genotoxin shown to be one of the potential precursors of inflammation-induced colorectal cancer and has also been linked to the hyper-virulence of other bacterial species (such as Klebsiella pneumonia – responsible for bacterial meningitis). Genotoxins are known for causing DNA mutations that, oftentimes, lead to cancer. The part of the bacterial genome responsible for the production of the genotoxin colibactin in certain strains of E. coli (of phylogenetic group B2) is known as the pks genomic island. Cells exposed to E. coli with this pks genomic island showed a marked increase in the frequency of genetic mutations, leading researchers to believe that this may contribute to the development of colonic tumors in colonized patients.
Bacteroides fragilis toxin, also known as fragilysin, is an enterotoxin responsible for the activation of E-cadherin. E-cadherin is a tumor suppressor protein that, when cleaved, increases the permeability of the intestinal barrier, thereby reducing its functionality. When the cellular adhesion within the tissue is decreased, it allows for infiltration of cancer cells into surrounding tissues. Cleavage of E-cadherin may also lead to overexpression of β-catenin, an adhesion and gene transcription protein, which has been associated with colorectal and other cancers.
Both Bacteroides spp. and E. coli have been found in increased numbers in patients with irritable bowel disease (IBD). Increased numbers of Lactobacillus spp. are associated with a decreased occurrence of IBD, thus encouraging the practice of taking probiotic supplements that contain that organism. Additionally, increased numbers of Bacteroides spp are found in those that consume more animal protein, as opposed to vegans.
Seeing that both colibactin and Bacteroides fragilis toxin are potential contributing factors leading to increased inflammation and tumorigenesis, one can certainly speculate that, when combined, the effect may be intensified. This is even more true of patients with FAP, who are commonly colonized with both oncotoxin producing bacterial strains, though it is not known if biofilms are present before polyps form. If biofilms are found to be present before polyp formation and are detected by way of stool analysis, this may give doctors the head start they need for a less invasive solution for colorectal tumor prevention.
By Sara Hylton and Andre Hsiung
Technical Services department of Hardy Diagnostics