Microbiota organization is a distinct feature of proximal colorectal cancers

Dejea, C.M. and Wick, E.C. and Hechenbleikner, E.M. and White, J.R. and Welch, J.L.M. and Rossetti, B.J. and Peterson, S.N. and Snesrud, E.C. and Borisy, G.G. and Lazarev, M. and Stein, E. and Vadivelu, J. and Roslani, A.C. and Malik, A.A. and Wanyiri, J.W. and Goh, K.L. and Thevambiga, I. and Fu, K. and Wan, F. and Llosa, N. and Housseau, F. and Romans, K. and Wu, X.Q. and McAllister, F.M. and Wu, S. and Vogelstein, B. and Kinzler, K.W. and Pardoll, D.M. and 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 (PNAS) ISSN 1091-6490, 111 (51). pp. 18321-18326.

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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.

Item Type: Article
Uncontrolled Keywords: Colorectal cancer; microbiome; biofilm; bacterial communities; adenoma
Subjects: R Medicine
Depositing User: MR Faizal II H
Date Deposited: 29 Dec 2015 01:54
Last Modified: 29 Dec 2015 01:54
URI: http://eprints.um.edu.my/id/eprint/15386

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