Affiliations 

  • 1 Departments of Microbiology and Immunology and
  • 2 Departments of Surgery
  • 3 Medicine, and
  • 4 Departments of Surgery and
  • 5 Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins Medical Institutions, Baltimore, MD 21287; Department of Oncology and Hopkins-Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD 21287; and
  • 6 Department of Oncology and Hopkins-Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD 21287; and
  • 7 Ludwig Center and Howard Hughes Medical Institute, Hopkins-Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD 21287
  • 8 Medicine, and Department of Oncology and Hopkins-Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD 21287; and
  • 9 Departments of Microbiology and Immunology and Medicine, and Department of Oncology and Hopkins-Kimmel Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD 21287; and csears@jhmi.edu
Proc Natl Acad Sci U S A, 2014 Dec 23;111(51):18321-6.
PMID: 25489084 DOI: 10.1073/pnas.1406199111

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.