Microbiota organization is a distinct feature of proximal colorectal cancers
- PMID: 25489084
- PMCID: PMC4280621
- DOI: 10.1073/pnas.1406199111
Microbiota organization is a distinct feature of proximal colorectal cancers
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 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.
Keywords: adenoma; bacterial communities; biofilm; colorectal cancer; microbiome.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
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Comment in
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Gut microbiota. Microbiota organization--a key to understanding CRC development.Nat Rev Gastroenterol Hepatol. 2015 Mar;12(3):128-9. doi: 10.1038/nrgastro.2015.25. Epub 2015 Feb 17. Nat Rev Gastroenterol Hepatol. 2015. PMID: 25688055
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