Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria

Science. 2018 Feb 2;359(6375):592-597. doi: 10.1126/science.aah3648. Epub 2018 Feb 1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli / microbiology*
  • Adenomatous Polyposis Coli / pathology*
  • Animals
  • Bacterial Toxins / genetics
  • Bacteroides fragilis / genetics
  • Bacteroides fragilis / isolation & purification
  • Bacteroides fragilis / pathogenicity*
  • Biofilms*
  • Carcinogenesis*
  • Colon / microbiology*
  • Colon / pathology
  • Colonic Neoplasms / microbiology*
  • Colonic Neoplasms / pathology
  • DNA Damage
  • Escherichia coli / genetics
  • Escherichia coli / isolation & purification
  • Escherichia coli / pathogenicity*
  • Gastrointestinal Microbiome
  • Humans
  • Interleukin-17 / analysis*
  • Intestinal Mucosa / chemistry
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism
  • Mice
  • Peptides / genetics
  • Peptides / metabolism
  • Polyketides
  • Precancerous Conditions / microbiology

Substances

  • Bacterial Toxins
  • IL17A protein, human
  • Interleukin-17
  • Peptides
  • Polyketides
  • colibactin
  • Bacteroides fragilis toxin
  • Metalloendopeptidases