Patients with Familial Adenomatous Polyposis Harbor Colonic Biofilms Containing Tumorigenic Bacteria

Overview

Journal Science

Specialty Science

Date 2018 Feb 9

PMID 29420293

Citations 535

Authors

Christine M Dejea

Payam Fathi

John M Craig

Annemarie Boleij

Rahwa Taddese

Abby L Geis

Xinqun Wu

Christina E DeStefano Shields

Elizabeth M Hechenbleikner

David L Huso

Robert A Anders

Francis M Giardiello

Elizabeth C Wick

Hao Wang

Shaoguang Wu

Drew M Pardoll

Franck Housseau

Cynthia L Sears

Affiliations

Soon will be listed here.

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 and Genes for colibactin () and toxin (), encoding secreted oncotoxins, were highly enriched in FAP patients' colonic mucosa compared to healthy individuals. Tumor-prone mice cocolonized with (expressing colibactin), and enterotoxigenic 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.

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References

Prorok-Hamon M, Friswell M, Alswied A, Roberts C, Song F, Flanagan P . Colonic mucosa-associated diffusely adherent afaC+ Escherichia coli expressing lpfA and pks are increased in inflammatory bowel disease and colon cancer. Gut. 2013; 63(5):761-70. PMC: 3995253. DOI: 10.1136/gutjnl-2013-304739. View

Boleij A, Hechenbleikner E, Goodwin A, Badani R, Stein E, Lazarev M . The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients. Clin Infect Dis. 2014; 60(2):208-15. PMC: 4351371. DOI: 10.1093/cid/ciu787. View

Johnson C, Dejea C, Edler D, Hoang L, Santidrian A, Felding B . Metabolism links bacterial biofilms and colon carcinogenesis. Cell Metab. 2015; 21(6):891-7. PMC: 4456201. DOI: 10.1016/j.cmet.2015.04.011. View

Martinez-Medina M, Mora A, Blanco M, Lopez C, Alonso M, Bonacorsi S . Similarity and divergence among adherent-invasive Escherichia coli and extraintestinal pathogenic E. coli strains. J Clin Microbiol. 2009; 47(12):3968-79. PMC: 2786640. DOI: 10.1128/JCM.01484-09. View

Giardiello F, KRUSH A, Petersen G, Booker S, Kerr M, Tong L . Phenotypic variability of familial adenomatous polyposis in 11 unrelated families with identical APC gene mutation. Gastroenterology. 1994; 106(6):1542-7. DOI: 10.1016/0016-5085(94)90408-1. View

Swidsinski A, Loening-Baucke V, Theissig F, Engelhardt H, Bengmark S, Koch S . Comparative study of the intestinal mucus barrier in normal and inflamed colon. Gut. 2006; 56(3):343-50. PMC: 1856798. DOI: 10.1136/gut.2006.098160. View

Swidsinski A, Loening-Baucke V, Herber A . Mucosal flora in Crohn's disease and ulcerative colitis - an overview. J Physiol Pharmacol. 2010; 60 Suppl 6:61-71. View

Son J, Khair S, Pettet 3rd D, Ouyang N, Tian X, Zhang Y . Altered Interactions between the Gut Microbiome and Colonic Mucosa Precede Polyposis in APCMin/+ Mice. PLoS One. 2015; 10(6):e0127985. PMC: 4485894. DOI: 10.1371/journal.pone.0127985. View

Prindiville T, Sheikh R, Cohen S, Tang Y, Cantrell M, Silva Jr J . Bacteroides fragilis enterotoxin gene sequences in patients with inflammatory bowel disease. Emerg Infect Dis. 2000; 6(2):171-4. PMC: 2640860. DOI: 10.3201/eid0602.000210. View

10.

Dejea C, Wick E, Sears C . Bacterial oncogenesis in the colon. Future Microbiol. 2013; 8(4):445-60. PMC: 4052711. DOI: 10.2217/fmb.13.17. View

11.

Fearon E, Vogelstein B . A genetic model for colorectal tumorigenesis. Cell. 1990; 61(5):759-67. DOI: 10.1016/0092-8674(90)90186-i. View

12.

Dejea C, Wick E, Hechenbleikner E, White J, Welch J, Rossetti B . Microbiota organization is a distinct feature of proximal colorectal cancers. Proc Natl Acad Sci U S A. 2014; 111(51):18321-6. PMC: 4280621. DOI: 10.1073/pnas.1406199111. View

13.

Arthur J, Perez-Chanona E, Muhlbauer M, Tomkovich S, Uronis J, Fan T . Intestinal inflammation targets cancer-inducing activity of the microbiota. Science. 2012; 338(6103):120-3. PMC: 3645302. DOI: 10.1126/science.1224820. View

14.

Wu S, Rhee K, Albesiano E, Rabizadeh S, Wu X, Yen H . A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 2009; 15(9):1016-22. PMC: 3034219. DOI: 10.1038/nm.2015. View