Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published November 2018 | Published + Supplemental Material
Journal Article Open

The Protective Role of Bacteroides fragilis in a Murine Model of Colitis-Associated Colorectal Cancer

Abstract

Many patients with chronic inflammation of the gut, such as that observed in inflammatory bowel disease (IBD), develop colorectal cancer (CRC). Recent studies have reported that the development of IBD and CRC partly results from an imbalanced composition of intestinal microbiota and that intestinal inflammation in these diseases can be modulated by the microbiota. The human commensal Bacteroides fragilis is best exemplified playing a protective role against the development of experimental colitis in several animal disease models. In this study, we found that gut inflammation caused by dextran sulfate sodium (DSS) treatment was inhibited by B. fragilis colonization in mice. Further, we reveal a protective role of B. fragilis treatment against colon tumorigenesis using an azoxymethane (AOM)/DSS-induced model of colitis-associated colon cancer in mice and demonstrate that the decreased tumorigenesis by B. fragilis administration is accompanied by inhibited expression of C-C chemokine receptor 5 (CCR5) in the gut. We show direct evidence that the inhibition of tumor formation provided by B. fragilis in colitis-associated CRC animals was dependent on the production of polysaccharide A (PSA) from B. fragilis and that Toll-like receptor 2 (TLR2) signaling was responsible for the protective function of B. fragilis.

Additional Information

© 2018 Lee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Received October 25, 2018; Accepted October 26, 2018. We thank Gregory W. Lawson (University of California, Los Angeles) for help with colitis histopathology and T. Thron, A. Maskell, and K. Ly for animal care. This work was supported by a Caltech postdoctoral fellowship; grants from the National Research Foundation of Korea (2017M2A2A6A01020874 and 2017M3A9F3043849) to Y.K.L.; and grants from the Crohn's and Colitis Foundation, the GIST-Caltech Collaboration, the Emerald Foundation, the Heritage Medical Research Institute, and the NIH (DK078938) to S.K.M. Y.K.L. designed and performed the experiments and analyzed the data. Y.K.L. and S.K.M. wrote the manuscript. P.M., S.B., and J.S. assisted in performing some experiments. W.-L.W. performed immunohistochemistry, and S.V. contributed to CRC tissue analysis. S.K.M. and Y.K.L. supervised the work. We declare no conflict of interest related to this work.

Attached Files

Published - e00587-18.full.pdf

Supplemental Material - inline-supplementary-material-1.pdf

Supplemental Material - inline-supplementary-material-2.pdf

Files

e00587-18.full.pdf
Files (2.5 MB)
Name Size Download all
md5:7fc4a897e44345624f297a975d4dfcba
1.2 MB Preview Download
md5:1ee92a95bcc2c0f639441871502d4b18
210.9 kB Preview Download
md5:a1934acb01d52bc8ce815928a21907f8
1.0 MB Preview Download

Additional details

Created:
August 22, 2023
Modified:
October 19, 2023