Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria.

Dejea CM, Fathi P, Craig JM, Boleij A, Taddese R, Geis AL, Wu X, DeStefano Shields CE, Hechenbleikner EM, Huso DL, Anders RA, Giardiello FM, Wick EC, Wang H, Wu S, Pardoll DM, Housseau F, Sears CL
Science. 2018 359 (6375): 592-597

PMID: 29420293 · PMCID: PMC5881113 · DOI:10.1126/science.aah3648

Individuals with sporadic colorectal cancer (CRC) frequently harbor abnormalities in the composition of the gut microbiome; however, the microbiota associated with precancerous lesions in hereditary CRC remains largely unknown. We studied colonic mucosa of patients with familial adenomatous polyposis (FAP), who develop benign precursor lesions (polyps) early in life. We identified patchy bacterial biofilms composed predominately of and Genes for colibactin () and toxin (), encoding secreted oncotoxins, were highly enriched in FAP patients' colonic mucosa compared to healthy individuals. Tumor-prone mice cocolonized with (expressing colibactin), and enterotoxigenic showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacterial strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.

Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

MeSH Terms (19)

Adenomatous Polyposis Coli Animals Bacterial Toxins Bacteroides fragilis Biofilms Carcinogenesis Colon Colonic Neoplasms DNA Damage Escherichia coli Gastrointestinal Microbiome Humans Interleukin-17 Intestinal Mucosa Metalloendopeptidases Mice Peptides Polyketides Precancerous Conditions

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