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

Soonjae Hwang; Chang Gun Lee; Minjeong Jo; Chan Oh Park; Sun Yeong Gwon; Samnoh Hwang; Hye Chin Yi; So Yeon Lee; Yong Bin Eom; Baktiar Karim; Ki Jong Rhee

doi:10.7150/ijms.38371

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

Soonjae Hwang, Chang Gun Lee, Minjeong Jo, Chan Oh Park, Sun Yeong Gwon, Samnoh Hwang, Hye Chin Yi, So Yeon Lee, Yong Bin Eom, Baktiar Karim, Ki Jong Rhee

Biomedical Laboratory Science

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	145-152
Number of pages	8
Journal	International Journal of Medical Sciences
Volume	17
Issue number	2
DOIs	https://doi.org/10.7150/ijms.38371
Publication status	Published - 2020

Bibliographical note

Funding Information:
Supplementary figures. http://www.medsci.org/v17p0145s1.pdf Acknowledgements This work was supported by NRF (National Research Foundation of Korea) Grant funded by the Ministry of Education (2017R1D1A1A02018088 and NRF-2017R1D1A1B03032960), and NRF-2017-Fostering Core Leaders of the Future Basic Science Program /Global Ph.D. Fellowship Program, 2017H1A2A10457 27. In addition, this work was supported in part by the Yonsei University Wonju Campus Future-Leading Research Initiative of 2017 (2017-52-0078). This work was supported in part by the Yonsei University Research Fund of 2019.

Funding Information:
This work was supported by NRF (National Research Foundation of Korea) Grant funded by the Ministry of Education (2017R1D1A1A02018088 and NRF-2017R1D1A1B03032960), and NRF-2017-Foster-ing Core Leaders of the Future Basic Science Program /Global Ph.D. Fellowship Program, 2017H1A2A10457 27. In addition, this work was supported in part by the Yonsei University Wonju Campus Future-Leading Research Initiative of 2017 (2017-52-0078). This work was supported in part by the Yonsei University Research Fund of 2019.

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© The author(s).

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Medicine(all)

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title = "Enterotoxigenic bacteroides fragilis infection exacerbates tumorigenesis in AOM/DSS mouse model",

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.",

author = "Soonjae Hwang and Lee, {Chang Gun} and Minjeong Jo and Park, {Chan Oh} and Gwon, {Sun Yeong} and Samnoh Hwang and Yi, {Hye Chin} and Lee, {So Yeon} and Eom, {Yong Bin} and Baktiar Karim and Rhee, {Ki Jong}",

note = "Funding Information: Supplementary figures. http://www.medsci.org/v17p0145s1.pdf Acknowledgements This work was supported by NRF (National Research Foundation of Korea) Grant funded by the Ministry of Education (2017R1D1A1A02018088 and NRF-2017R1D1A1B03032960), and NRF-2017-Fostering Core Leaders of the Future Basic Science Program /Global Ph.D. Fellowship Program, 2017H1A2A10457 27. In addition, this work was supported in part by the Yonsei University Wonju Campus Future-Leading Research Initiative of 2017 (2017-52-0078). This work was supported in part by the Yonsei University Research Fund of 2019. Funding Information: This work was supported by NRF (National Research Foundation of Korea) Grant funded by the Ministry of Education (2017R1D1A1A02018088 and NRF-2017R1D1A1B03032960), and NRF-2017-Foster-ing Core Leaders of the Future Basic Science Program /Global Ph.D. Fellowship Program, 2017H1A2A10457 27. In addition, this work was supported in part by the Yonsei University Wonju Campus Future-Leading Research Initiative of 2017 (2017-52-0078). This work was supported in part by the Yonsei University Research Fund of 2019. Publisher Copyright: {\textcopyright} The author(s).",

year = "2020",

doi = "10.7150/ijms.38371",

language = "English",

volume = "17",

pages = "145--152",

journal = "International Journal of Medical Sciences",

issn = "1449-1907",

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TY - JOUR

T1 - Enterotoxigenic bacteroides fragilis infection exacerbates tumorigenesis in AOM/DSS mouse model

AU - Hwang, Soonjae

AU - Lee, Chang Gun

AU - Jo, Minjeong

AU - Park, Chan Oh

AU - Gwon, Sun Yeong

AU - Hwang, Samnoh

AU - Yi, Hye Chin

AU - Lee, So Yeon

AU - Eom, Yong Bin

AU - Karim, Baktiar

AU - Rhee, Ki Jong

N1 - Funding Information: Supplementary figures. http://www.medsci.org/v17p0145s1.pdf Acknowledgements This work was supported by NRF (National Research Foundation of Korea) Grant funded by the Ministry of Education (2017R1D1A1A02018088 and NRF-2017R1D1A1B03032960), and NRF-2017-Fostering Core Leaders of the Future Basic Science Program /Global Ph.D. Fellowship Program, 2017H1A2A10457 27. In addition, this work was supported in part by the Yonsei University Wonju Campus Future-Leading Research Initiative of 2017 (2017-52-0078). This work was supported in part by the Yonsei University Research Fund of 2019. Funding Information: This work was supported by NRF (National Research Foundation of Korea) Grant funded by the Ministry of Education (2017R1D1A1A02018088 and NRF-2017R1D1A1B03032960), and NRF-2017-Foster-ing Core Leaders of the Future Basic Science Program /Global Ph.D. Fellowship Program, 2017H1A2A10457 27. In addition, this work was supported in part by the Yonsei University Wonju Campus Future-Leading Research Initiative of 2017 (2017-52-0078). This work was supported in part by the Yonsei University Research Fund of 2019. Publisher Copyright: © The author(s).

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

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M3 - Article

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JO - International Journal of Medical Sciences

JF - International Journal of Medical Sciences

SN - 1449-1907

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

Abstract

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