Format

Send to

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

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

Author information

1
Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA.
2
Department of Oncology, Johns Hopkins University, Baltimore, MD, USA.
3
Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
4
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
5
Department of Pathology, Radboud University Medical Center, Postbus 9101, 6500 HB Nijmegen, Netherlands.
6
Department of Surgery, Johns Hopkins University, Baltimore, MD, USA.
7
Department of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, USA.
8
Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
9
Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA. csears@jhmi.edu.

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.

PMID:
29420293
PMCID:
PMC5881113
DOI:
10.1126/science.aah3648
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center