The way in which microbial communities are organized in the mucosa of the colon could be a critical factor in the development of some colorectal cancers, researchers said.
The presence of bacterial biofilms – collections of microbial communities encased in a polymeric matrix – was associated with a fivefold higher risk of developing colorectal cancer, compared with individuals without biofilms, the international team of researchers reported in the Proceedings of the National Academy of Sciences.
Writing in background information to their paper, Christine M. Dejea of the departments of microbiology and immunology at the Johns Hopkins Medical Institutions, Baltimore, and associates noted that biofilms characterize many chronic mucosal diseases like inflammatory bowel disease, otitis media, and rhinosinusitus. Until now, however, they haven’t been associated with colorectal cancer (Proc. Natl. Acad. Sci. U. S. A. 2015;111:18321-26).
The researchers systematically studied healthy and cancerous tissue biopsies from 118 people who were undergoing surgery or colonoscopy at the Johns Hopkins Hospital or the University of Malaya Medical Centre in Kuala Lumpur, Malaysia.
They identified invasive polymicrobial bacterial biofilms structures on 89% of right-side tumors (13 of 15 CRCs, 4 of 4 adenomas) and 12% of left-side tumors (2 of 15 CRCs, 0 of 2 adenomas).
Patients with biofilm-positive tumors, whether they were CRCs or adenomas, all had biofilms on their tumor-free mucosa far distant from their tumors. None of the normal mucosa from patients with biofilm-negative CRCs possessed a biofilm, the investigators said.
Biofilm formation in both the colon cancer host and healthy subjects was associated with a reduced or redistributed colonic epithelial cell E-cadherin, consistent with increased epithelial permeability.
The inflammatory marker IL-6 also was enhanced with biofilm formation, even in healthy patients without CRC, suggesting that early biofilm formation can initiate procarcinogenic tissue inflammation, the researchers said.
“Our data support a model whereby biofilm formation enhances epithelial permeability that increases direct access of bacterial antigens/mutagens to an unshielded epithelial surface and promotes procarcinogenic tissue inflammation,” they wrote.
The findings also introduce the concept that the organization, as opposed to the composition per se, of the mucosa-associated microbial community is an important factor in CRC pathogenesis, particularly in the proximal colon, they said.
The authors speculated “that colorectal cancers develop in two different settings: individuals with biofilms and individuals without them.”
“Based on the data described here, the risk of developing CRC is more than fivefold higher in the patients with biofilms compared with those without biofilms,” they wrote.
The study authors suggest that the new findings could be used to develop a noninvasive test that detects these biofilms.
Probiotic therapies also could potentially eliminate them, they said.
The National Institutes of Health supported the study. The authors declared no conflicts of interest.