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 language | English (US) |
|---|---|
| Pages (from-to) | 592-597 |
| Number of pages | 6 |
| Journal | Science |
| Volume | 359 |
| Issue number | 6375 |
| DOIs | |
| State | Published - Feb 2 2018 |
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ASJC Scopus subject areas
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Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. / Dejea, Christine M.; Fathi, Payam; Craig, John M.; Boleij, Annemarie; Taddese, Rahwa; Geis, Abby; Wu, Xinqun; DeStefano Shields, Christina E.; Hechenbleikner, Elizabeth M.; Huso, David L.; Anders, Robert A; Giardiello, Francis M; Wick, Elizabeth C.; Wang, Hao; Wu, Shaoguang; Pardoll, Andrew Mark; Housseau, Franck; Sears, Cynthia Louise.
In: Science, Vol. 359, No. 6375, 02.02.2018, p. 592-597.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria
AU - Dejea, Christine M.
AU - Fathi, Payam
AU - Craig, John M.
AU - Boleij, Annemarie
AU - Taddese, Rahwa
AU - Geis, Abby
AU - Wu, Xinqun
AU - DeStefano Shields, Christina E.
AU - Hechenbleikner, Elizabeth M.
AU - Huso, David L.
AU - Anders, Robert A
AU - Giardiello, Francis M
AU - Wick, Elizabeth C.
AU - Wang, Hao
AU - Wu, Shaoguang
AU - Pardoll, Andrew Mark
AU - Housseau, Franck
AU - Sears, Cynthia Louise
PY - 2018/2/2
Y1 - 2018/2/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85041288837&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85041288837&partnerID=8YFLogxK
U2 - 10.1126/science.aah3648
DO - 10.1126/science.aah3648
M3 - Article
VL - 359
SP - 592
EP - 597
JO - Science
JF - Science
SN - 0036-8075
IS - 6375
ER -