Details

Autor(en) / Beteiligte

• Dejea, Christine M.
• Wick, Elizabeth C.
• Hechenbleikner, Elizabeth M.
• White, James R.
• Welch, Jessica L. Mark
• Rossetti, Blair J.
• Peterson, Scott N.
• Snesrud, Erik C.
• Borisy, Gary G.
• Lazarev, Mark
• Stein, Ellen
• Vadivelu, Jamuna
• Roslani, April C.
• Malik, Ausuma A.
• Wanyiri, Jane W.
• Goh, Khean L.
• Thevambiga, Iyadorai
• Fu, Kai
• Wan, Fengyi
• Llosa, Nicolas
• Housseau, Franck
• Romans, Katharine
• Wu, XinQun
• McAllister, Florencia M.
• Wu, Shaoguang
• Vogelstein, Bert
• Kinzler, Kenneth W.
• Pardoll, Drew M.
• Sears, Cynthia L.

Titel

Microbiota organization is a distinct feature of proximal colorectal cancers

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2014-12, Vol.111 (51), p.18321-18326

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• Environmental factors clearly affect colorectal cancer (CRC) incidence, but the mechanisms through which these factors function are unknown. One prime candidate is an altered colonic microbiota. Here we show that the mucosal microbiota organization is a critical factor associated with a subset of CRC. We identified invasive polymicrobial bacterial biofilms (bacterial aggregates), structures previously associated with nonmalignant intestinal pathology, nearly universally (89%) on right-sided tumors (13 of 15 CRCs, 4 of 4 adenomas) but on only 12% of left-sided tumors (2 of 15 CRCs, 0 of 2 adenomas). Surprisingly, patients with biofilm-positive tumors, whether cancers or adenomas, all had biofilms on their tumor-free mucosa far distant from their tumors. 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. High-throughput sequencing revealed no consistent bacterial genus associated with tumors, regardless of biofilm status. However, principal coordinates analysis revealed that biofilm communities on paired normal mucosa, distant from the tumor itself, cluster with tumor microbiomes as opposed to biofilm-negative normal mucosa bacterial communities also from the tumor host. Colon mucosal biofilm detection may predict increased risk for development of sporadic CRC. Significance We demonstrate, to our knowledge for the first time, that bacterial biofilms are associated with colorectal cancers, one of the leading malignancies in the United States and abroad. Colon biofilms, dense communities of bacteria encased in a likely complex matrix that contact the colon epithelial cells, are nearly universal on right colon tumors. Most remarkably, biofilm presence correlates with bacterial tissue invasion and changes in tissue biology with enhanced cellular proliferation, a basic feature of oncogenic transformation occurring even in colons without evidence of cancer. Microbiome profiling revealed that biofilm communities on paired normal mucosa cluster with tumor microbiomes but lack distinct taxa differences. This work introduces a previously unidentified concept whereby microbial community structural organization exhibits the potential to contribute to disease progression.