For reasons unknown, dense mats of interacting bacteria—biofilms—constitute a near-universal feature of tumors that appear in the “right” or ascending colon, but are much less prevalent in tumors that appear in the “left” or descending colon. Whatever might explain the disparity, say researchers, the newfound association between biofilms and at least some colon tumors suggests the basis of a new diagnostic test. Such a test could even take advantage of an imaging technique—combinatorial imaging—researchers developed to “see” microbial community structure.

In an examination of healthy and cancerous tissue biopsied from 118 people undergoing surgery or colonoscopy at The Johns Hopkins Hospital or at the University of Malaya Medical Centre in Malaysia, researchers led by Johns Hopkins’ Cynthia L. Sears, M.D., found that biofilms were present on 89% of tumors—13 of 15 cancers and four of four polyps—removed from the right colon. By contrast, biofilms were found only 12% of the time on tumors on the left side of the colon—2 of 15 cancers and no polyps.

Overall, the researchers say, their data suggest the risk of developing colorectal cancer might be fivefold higher in patients with biofilms on the right side of the colon, compared to patients without the bacterial mats. Results of their work were published online December 8 in the Proceedings of the National Academy of Sciences (PNAS), in an article entitled, “Microbiota organization is a distinct feature of proximal colorectal cancers.”

In the study, the scientists found a link between the presence of biofilms and biological changes associated with increased cell growth in the biopsied tissues. The researchers also identified the types of bacteria found in the colon tissues through genetic sequencing. They found that the same species of bacteria were present in tumors from people with and without biofilms. This suggests that the biofilm itself, rather than a particular kind of bacteria, may be the cancer-causing trigger.

“Bacterial biofilms were associated with diminished colonic epithelial cell E-cadherin and enhanced epithelial cell IL-6 and Stat3 activation, as well as increased crypt epithelial cell proliferation in normal colon mucosa,” wrote the authors of the PNAS paper. “High-throughput sequencing revealed no consistent bacterial genus associated with tumors, regardless of biofilm status.”

The authors concluded that “colon mucosal biofilm detection may predict increased risk for development of sporadic colorectal cancer.” Paper co-authors from the Marine Biological Laboratory (MBL) including Jessica Mark Welch, Ph.D., added that detection efforts could take advantage of the combinatorial imaging technique used in the current study.

The MBL scientists indicated that their methodology uses different colors of fluorescent probes to “light up” different species of bacteria in a biofilm, revealing the 3D structure of its microbial community. In the current study, the researchers used nine probes to determine that the biofilms associated with ascending colon tumors are composed of many species of bacteria. The researchers also found that these species are diverse (non-identical) and that the part of the biofilm that invades the mucosal layer contains a subset of all the bacterial strains in the biofilm, rather than just one invading strain.

Dr. Sears and her team speculate that biofilms induce inflammation, which in turn spurs genetic mutations in epithelial cells that make them prone to becoming cancerous. Dr. Sears' earlier research looked at the role of bacteria and diarrheal disease, “but over time we recognized that our bacteria triggered changes in cells that were consistent with the ability to induce tumors,” she explained. “And we wondered whether colonization with these organisms might be a long-term trigger for colon cancer.”

In the current study, the scientists found a link between the presence of biofilms and biological changes associated with increased cell growth in the biopsied tissues. The researchers plan to examine biofilms in subjects over at least five years, Dr. Sears says, “to see if we can understand the dynamics of their formation, persistence and relationship to early cancer development.”

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