Reduction of Murine Colon Tumorigenesis Driven by Enterotoxigenic Bacteroides fragilis Using Cefoxitin Treatment

Christina E. Destefano Shields, Sara W. Van Meerbeke, Franck Housseau, Hao Wang, David L. Huso, Robert A. Casero, Heather O'Hagan, Cynthia L. Sears

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background. Chronic inflammation and composition of the colon microbiota have been associated with colorectal cancer in humans. The human commensal enterotoxigenic Bacteroides fragilis (ETBF) is linked to both inflammatory bowel disease and colorectal cancer and, in our murine model, causes interleukin 17A (IL-17A)-dependent colon tumors. In these studies, we hypothesized that persistent colonization by ETBF is required for tumorigenesis. Methods. We established a method for clearing ETBF in mice, using the antibiotic cefoxitin. Multiple intestinal neoplasia mice were colonized with ETBF for the experiment duration or were cleared of infection after 5 or 14 days. Gross tumors and/or microadenomas were then evaluated. In parallel, IL-17A expression was evaluated in wild-type littermates. Results. Cefoxitin treatment resulted in complete and durable clearance of ETBF colonization. We observed a stepwise increase in median colon tumor numbers as the duration of ETBF colonization increased before cefoxitin treatment. ETBF eradication also significantly decreased mucosal IL-17A expression. Conclusions. The timing of ETBF clearance profoundly influences colon adenoma formation, defining a period during which the colon is susceptible to IL-17A-dependent tumorigenesis in this murine model. This model system can be used to study the microbiota-dependent and molecular mechanisms contributing to IL-17A-dependent colon tumor initiation.

Original languageEnglish (US)
Pages (from-to)122-129
Number of pages8
JournalJournal of Infectious Diseases
Volume214
Issue number1
DOIs
StatePublished - Jul 1 2016

Fingerprint

Cefoxitin
Bacteroides fragilis
Colon
Carcinogenesis
Interleukin-17
Microbiota
Neoplasms
Colorectal Neoplasms
Inflammatory Bowel Diseases
Adenoma
Anti-Bacterial Agents
Inflammation

Keywords

  • Colitis
  • Colon cancer
  • Enterotoxigenic Bacteroides fragilis
  • microbiota

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Destefano Shields, C. E., Van Meerbeke, S. W., Housseau, F., Wang, H., Huso, D. L., Casero, R. A., ... Sears, C. L. (2016). Reduction of Murine Colon Tumorigenesis Driven by Enterotoxigenic Bacteroides fragilis Using Cefoxitin Treatment. Journal of Infectious Diseases, 214(1), 122-129. https://doi.org/10.1093/infdis/jiw069

Reduction of Murine Colon Tumorigenesis Driven by Enterotoxigenic Bacteroides fragilis Using Cefoxitin Treatment. / Destefano Shields, Christina E.; Van Meerbeke, Sara W.; Housseau, Franck; Wang, Hao; Huso, David L.; Casero, Robert A.; O'Hagan, Heather; Sears, Cynthia L.

In: Journal of Infectious Diseases, Vol. 214, No. 1, 01.07.2016, p. 122-129.

Research output: Contribution to journalArticle

Destefano Shields, CE, Van Meerbeke, SW, Housseau, F, Wang, H, Huso, DL, Casero, RA, O'Hagan, H & Sears, CL 2016, 'Reduction of Murine Colon Tumorigenesis Driven by Enterotoxigenic Bacteroides fragilis Using Cefoxitin Treatment', Journal of Infectious Diseases, vol. 214, no. 1, pp. 122-129. https://doi.org/10.1093/infdis/jiw069
Destefano Shields, Christina E. ; Van Meerbeke, Sara W. ; Housseau, Franck ; Wang, Hao ; Huso, David L. ; Casero, Robert A. ; O'Hagan, Heather ; Sears, Cynthia L. / Reduction of Murine Colon Tumorigenesis Driven by Enterotoxigenic Bacteroides fragilis Using Cefoxitin Treatment. In: Journal of Infectious Diseases. 2016 ; Vol. 214, No. 1. pp. 122-129.
@article{2f011be085334625bff5154fb4481043,
title = "Reduction of Murine Colon Tumorigenesis Driven by Enterotoxigenic Bacteroides fragilis Using Cefoxitin Treatment",
abstract = "Background. Chronic inflammation and composition of the colon microbiota have been associated with colorectal cancer in humans. The human commensal enterotoxigenic Bacteroides fragilis (ETBF) is linked to both inflammatory bowel disease and colorectal cancer and, in our murine model, causes interleukin 17A (IL-17A)-dependent colon tumors. In these studies, we hypothesized that persistent colonization by ETBF is required for tumorigenesis. Methods. We established a method for clearing ETBF in mice, using the antibiotic cefoxitin. Multiple intestinal neoplasia mice were colonized with ETBF for the experiment duration or were cleared of infection after 5 or 14 days. Gross tumors and/or microadenomas were then evaluated. In parallel, IL-17A expression was evaluated in wild-type littermates. Results. Cefoxitin treatment resulted in complete and durable clearance of ETBF colonization. We observed a stepwise increase in median colon tumor numbers as the duration of ETBF colonization increased before cefoxitin treatment. ETBF eradication also significantly decreased mucosal IL-17A expression. Conclusions. The timing of ETBF clearance profoundly influences colon adenoma formation, defining a period during which the colon is susceptible to IL-17A-dependent tumorigenesis in this murine model. This model system can be used to study the microbiota-dependent and molecular mechanisms contributing to IL-17A-dependent colon tumor initiation.",
keywords = "Colitis, Colon cancer, Enterotoxigenic Bacteroides fragilis, microbiota",
author = "{Destefano Shields}, {Christina E.} and {Van Meerbeke}, {Sara W.} and Franck Housseau and Hao Wang and Huso, {David L.} and Casero, {Robert A.} and Heather O'Hagan and Sears, {Cynthia L.}",
year = "2016",
month = "7",
day = "1",
doi = "10.1093/infdis/jiw069",
language = "English (US)",
volume = "214",
pages = "122--129",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Reduction of Murine Colon Tumorigenesis Driven by Enterotoxigenic Bacteroides fragilis Using Cefoxitin Treatment

AU - Destefano Shields, Christina E.

AU - Van Meerbeke, Sara W.

AU - Housseau, Franck

AU - Wang, Hao

AU - Huso, David L.

AU - Casero, Robert A.

AU - O'Hagan, Heather

AU - Sears, Cynthia L.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Background. Chronic inflammation and composition of the colon microbiota have been associated with colorectal cancer in humans. The human commensal enterotoxigenic Bacteroides fragilis (ETBF) is linked to both inflammatory bowel disease and colorectal cancer and, in our murine model, causes interleukin 17A (IL-17A)-dependent colon tumors. In these studies, we hypothesized that persistent colonization by ETBF is required for tumorigenesis. Methods. We established a method for clearing ETBF in mice, using the antibiotic cefoxitin. Multiple intestinal neoplasia mice were colonized with ETBF for the experiment duration or were cleared of infection after 5 or 14 days. Gross tumors and/or microadenomas were then evaluated. In parallel, IL-17A expression was evaluated in wild-type littermates. Results. Cefoxitin treatment resulted in complete and durable clearance of ETBF colonization. We observed a stepwise increase in median colon tumor numbers as the duration of ETBF colonization increased before cefoxitin treatment. ETBF eradication also significantly decreased mucosal IL-17A expression. Conclusions. The timing of ETBF clearance profoundly influences colon adenoma formation, defining a period during which the colon is susceptible to IL-17A-dependent tumorigenesis in this murine model. This model system can be used to study the microbiota-dependent and molecular mechanisms contributing to IL-17A-dependent colon tumor initiation.

AB - Background. Chronic inflammation and composition of the colon microbiota have been associated with colorectal cancer in humans. The human commensal enterotoxigenic Bacteroides fragilis (ETBF) is linked to both inflammatory bowel disease and colorectal cancer and, in our murine model, causes interleukin 17A (IL-17A)-dependent colon tumors. In these studies, we hypothesized that persistent colonization by ETBF is required for tumorigenesis. Methods. We established a method for clearing ETBF in mice, using the antibiotic cefoxitin. Multiple intestinal neoplasia mice were colonized with ETBF for the experiment duration or were cleared of infection after 5 or 14 days. Gross tumors and/or microadenomas were then evaluated. In parallel, IL-17A expression was evaluated in wild-type littermates. Results. Cefoxitin treatment resulted in complete and durable clearance of ETBF colonization. We observed a stepwise increase in median colon tumor numbers as the duration of ETBF colonization increased before cefoxitin treatment. ETBF eradication also significantly decreased mucosal IL-17A expression. Conclusions. The timing of ETBF clearance profoundly influences colon adenoma formation, defining a period during which the colon is susceptible to IL-17A-dependent tumorigenesis in this murine model. This model system can be used to study the microbiota-dependent and molecular mechanisms contributing to IL-17A-dependent colon tumor initiation.

KW - Colitis

KW - Colon cancer

KW - Enterotoxigenic Bacteroides fragilis

KW - microbiota

UR - http://www.scopus.com/inward/record.url?scp=84979256218&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979256218&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiw069

DO - 10.1093/infdis/jiw069

M3 - Article

C2 - 26908749

AN - SCOPUS:84979256218

VL - 214

SP - 122

EP - 129

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 1

ER -