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Int J Med Sci. 2020 Jan 1;17(2):145-152. doi: 10.7150/ijms.38371. eCollection 2020.

Enterotoxigenic Bacteroides fragilis infection exacerbates tumorigenesis in AOM/DSS mouse model.

Author information

1
Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University at Wonju, Wonju, Gangwon-do 26493, Republic of Korea.
2
Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, 26426, Republic of Korea.
3
Department of Medical Science, College of Medical Sciences, Soonchunhyang University, Asan, Chungnam, 31538, Republic of Korea.
4
Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan, Chungnam, 31538, Republic of Korea.
5
Leidos Biomedical Research Inc, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, U.S.A.

Abstract

The azoxymethane (AOM)/dextran sulfate sodium (DSS) murine model is commonly used to study colitis-associated cancer. The human commensal bacterium, enterotoxigenic Bacteroides fragilis (ETBF) secretes the Bacteroides fragilis toxin (BFT) which is necessary and sufficient to cause colitis. We report that BALB/c mice infected with WT-ETBF and administered three cycles of AOM/DSS developed numerous, large-sized polyps predominantly in the colorectal region. In addition, AOM/DSS-treated BALB/c mice orally inoculated with wild-type nontoxigenic Bacteroides fragilis (WT-NTBF) overexpressing bft (rETBF) developed numerous polyps whereas mice infected with WT-NTBF overexpressing a biologically inactive bft (rNTBF) did not promote polyp formation. Unexpectedly, the combination of AOM+ETBF did not induce polyp formation whereas ETBF+DSS did induce polyp development in a subset of BALB/c mice. In conclusion, WT-ETBF promoted polyp development in AOM/DSS murine model with increased colitis in BALB/c mice. The model described herein provides an experimental platform for understanding ETBF-induced colonic tumorigenesis and studying colorectal cancer in wild-type mice.

KEYWORDS:

ETBF; azoxymethane; colorectal cancer; dextran sulfate sodium; inflammation

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

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