@article{5aefd6007b834ddeacf7efc79f7e1164,
title = "Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria",
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{\textquoteright} 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.",
author = "Dejea, {Christine M.} and Payam Fathi and Craig, {John M.} and Annemarie Boleij and Rahwa Taddese and Geis, {Abby L.} and Xinqun Wu and {DeStefano Shields}, {Christina E.} and Hechenbleikner, {Elizabeth M.} and Huso, {David L.} and Anders, {Robert A.} and Giardiello, {Francis M.} and Wick, {Elizabeth C.} and Hao Wang and Shaoguang Wu and Pardoll, {Drew M.} and Franck Housseau and Sears, {Cynthia L.}",
note = "Funding Information: We thank K. Kinzler and B. Vogelstein for valuable discussions; K. Romans and L. Hylind for assistance with patient enrollment; and S. Besharati for assistance with histopathologic analyses. The data presented in this manuscript are tabulated in the main text and supplementary materials and methods. This work was supported by the Bloomberg Philanthropies and by NIH grants R01 CA151393 (to C.L.S., D.M.P.), K08 DK087856 (to E.C.W.), 5T32CA126607-05 (to E.M.H.), P30 DK089502 (Johns Hopkins University School of Medicine), P30 CA006973 (Johns Hopkins University School of Medicine), and P50 CA62924 (Johns Hopkins University School of Medicine). Funding was also provided through a research agreement with Bristol-Myers Squibb Co-International Immuno-Oncology Network-IION Resource Model, 300-2344 (to D.M.P.); Alexander and Margaret Stewart Trust (Johns Hopkins University School of Medicine); GSRRIG-015 (American Society of Colon and Rectal Surgeons to E.M.H.); The Netherlands Organization for Scientific Research (NWO 825.11.03 and 016.166.089 to A.B.); and a grant from the Institute M{\'e}rieux (to C.L.S. and D.M.P.). D.M.P. discloses consultant relationships with Aduro Biotech, Amgen, Astra Zeneca, Bayer, Compugen, DNAtrix, Five Prime, GlaxoSmithKline, ImmuneXcite, Jounce Therapeutics, Neximmune, Pfizer, Rock Springs Capital, Sanofi, Tizona, Janssen, Merck, Astellas, Flx Bio, Ervaxx, and DNAX. D.M.P. receives research support from Bristol-Myers Squibb, Compugen, Ervaxx, and Potenza. D.M.P. is a scientific advisory board member for Immunomic Therapeutics. D.M.P. shares intellectual property with Aduro Biotech, Bristol-Myers Squibb, Compugen, and Immunomic Therapeutics. All other authors declare no competing interests. C.L.S., D.M.P., C.M.D., and E.C.W. are inventors on patent application PCT/US2014/ 055123 submitted by Johns Hopkins University that covers use of biofilm formation to define risk for colon cancer. Publisher Copyright: {\textcopyright} 2017 The Authors, some rights reserved.",
year = "2018",
month = feb,
day = "2",
doi = "10.1126/science.aah3648",
language = "English (US)",
volume = "359",
pages = "592--597",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6375",
}