Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria

Christine M. Dejea, Payam Fathi, John M. Craig, Annemarie Boleij, Rahwa Taddese, Abby Geis, Xinqun Wu, Christina E. DeStefano Shields, Elizabeth M. Hechenbleikner, David L Huso, Robert A. Anders, Francis M. Giardiello, Elizabeth C. Wick, Hao Wang, Shaoguang Wu, Drew M. Pardoll, Franck Housseau, Cynthia L. Sears

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Abstract

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 Escherichia coli and Bacteroides fragilis. Genes for colibactin (clbB) and Bacteroides fragilis toxin (bft), encoding secreted oncotoxins, were highly enriched in FAP patients’ colonic mucosa compared to healthy individuals. Tumor-prone mice cocolonized with E. coli (expressing colibactin), and enterotoxigenic B. fragilis 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.

Original languageEnglish (US)
Pages (from-to)592-597
Number of pages6
JournalScience
Volume359
Issue number6375
DOIs
StatePublished - Feb 2 2018

ASJC Scopus subject areas

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    Dejea, C. M., Fathi, P., Craig, J. M., Boleij, A., Taddese, R., Geis, A., Wu, X., DeStefano Shields, C. E., Hechenbleikner, E. M., Huso, D. L., Anders, R. A., Giardiello, F. M., Wick, E. C., Wang, H., Wu, S., Pardoll, D. M., Housseau, F., & Sears, C. L. (2018). Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science, 359(6375), 592-597. https://doi.org/10.1126/science.aah3648