Microbiota organization is a distinct feature of proximal colorectal cancers

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

Research output: Contribution to journalArticle

Abstract

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 biofilmpositive 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.

Original languageEnglish (US)
Pages (from-to)18321-18326
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number51
DOIs
StatePublished - Dec 23 2014

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Keywords

  • Adenoma
  • Bacterial communities
  • Biofilm
  • Colorectal cancer
  • Microbiome

ASJC Scopus subject areas

  • General

Cite this

Dejea, C. M., Wick, E. C., Hechenbleikner, E. M., White, J. R., Mark Welch, J. L., Rossettid, B. J., Peterson, S. N., Snesrud, E. C., Borisy, G. G., Lazarev, M., Stein, E., Vadivelu, J., Roslani, A. C., Malik, A. A., Wanyiri, J. W., Goh, K. L., Thevambiga, I., Fu, K., Wan, F., ... Sears, C. L. (2014). Microbiota organization is a distinct feature of proximal colorectal cancers. Proceedings of the National Academy of Sciences of the United States of America, 111(51), 18321-18326. https://doi.org/10.1073/pnas.1406199111