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

Research Paper

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

Soonjae Hwang1,2, Chang Gun Lee1, Minjeong Jo1, Chan Oh Park1, Sun-Yeong Gwon1, Samnoh Hwang1, Hye Chin Yi1, So-Yeon Lee3, Yong-Bin Eom3,4, Baktiar Karim5, Ki-Jong Rhee1✉

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.

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Citation:
Hwang S, Lee CG, Jo M, Park CO, Gwon SY, Hwang S, Yi HC, Lee SY, Eom YB, Karim B, Rhee KJ. Enterotoxigenic Bacteroides fragilis infection exacerbates tumorigenesis in AOM/DSS mouse model. Int J Med Sci 2020; 17(2):145-152. doi:10.7150/ijms.38371. Available from http://www.medsci.org/v17p0145.htm

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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, colorectal cancer, inflammation, azoxymethane, dextran sulfate sodium