Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria
By Christine M Dejea, Payam Fathi, J. Craig, A. Boleij, Rahwa Taddese, Abby L. Geis, Xinqun Wu, C. D. DeStefano Shields, Elizabeth M. Hechenbleikner, D. Huso and 8 more. Science, 2018
957 citations recorded by the source corpus.
Biofilms provide refuge for cancerous bacteria Familial adenomatous polyposis (FAP) causes benign polyps along the colon. If left untreated, FAP leads to a high incidence of colon cancer. To understand how polyps influence tumor formation, Dejea et al. examined the colonic mucosa of FAP patients. They discovered biofilms containing the carcinogenic versions of the bacterial species Escherichia coli and Bacteroides fragilis. Colon tissue from FAP patients exhibited greater expression of two bacterial genes that produce secreted oncotoxins. Studies in mice showed that specific bacteria could work together to induce colon inflammation and tumor formation. Science, this issue p. 592 Bacterial biofilms are linked to colon cancer. 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.
Subfields: Epidemiology, Pathology and Forensic Medicine, Surgery
View Paper: https://www.semanticscholar.org/paper/a95d2c9a009c8cd0945fd6d93744a64677c07dfb
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Epidemiology
In Pathology and Forensic Medicine
Citations in the corpus
- The IL-17 family of cytokines in health and disease (2019, background): “Mucus-invasive bacterial biofilms of B fragilis, F nucleatum, Peptostreptococcus stomatis, Gemella morbilliform, and Parvimonas micra associate with tumors in patients with familial adenomatous polyposis(Dejea et al., 2018; Dejea et al., 2014).”
- Gut Bacteroides species in health and disease (2021, background): “In addition, Bfr may enhance the colonization of certain enteric pathogens in individuals with hereditary conditions leading to the formation of certain cancer types.(135) Another mechanism that may lead to cancer formation in the colon involves biofilms produced by certain Bacteroides spp.”
- The microbiome and human cancer (2021, background): “fragilis–derived toxin (22, 37, 38, 40, 41); (ii) CagA-mediated or IL-17– producing gd T cell–mediated inflammation in stomach and lung cancers, respectively (18, 103); (iii) chemoresistance through direct microbial metabolism (cytidine deaminase degradation of gemcitabine) in pancreatic cancer or i”
- Inflammation and Cancer: Triggers, Mechanisms and Consequences (2019, background): “, 2017), ability to form biofilms and initiate the outgrowth of the consortia of invasive bacteria (Dejea et al., 2018; Tomkovich et al., 2019) or ability to induce low grade inflammation disrupting the barrier (Wu et al.”
- Bacterial Biofilm and its Role in the Pathogenesis of Disease (2020, background): “fragilis has been proposed as an initiator of colorectal cancer due to its ability to disturb the epithelial homeostasis and influence cell proliferation [96,97].”