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

Lee, Yun Kyung and Mehrabian, Parpi and Boyajian, Silva and Wu, Wei-Li and Selicha, Jane and Vonderfecht, Steven and Mazmanian, Sarkis K. (2018) The Protective Role of Bacteroides fragilis in a Murine Model of Colitis-Associated Colorectal Cancer. mSphere, 3 (6). Art. No. e00587-18. ISSN 2379-5042. PMCID PMC6236802. https://resolver.caltech.edu/CaltechAUTHORS:20181115-081127417

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1128/msphere.00587-18DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236802/PubMed CentralArticle
ORCID:
AuthorORCID
Wu, Wei-Li0000-0003-2610-1881
Mazmanian, Sarkis K.0000-0003-2713-1513
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.
Group:Heritage Medical Research Institute
Funders:
Funding AgencyGrant Number
CaltechUNSPECIFIED
National Research Foundation of Korea2017M2A2A6A01020874
National Research Foundation of Korea2017M3A9F3043849
Crohn’s and Colitis FoundationUNSPECIFIED
GIST-Caltech CollaborationUNSPECIFIED
Emerald FoundationUNSPECIFIED
Heritage Medical Research InstituteUNSPECIFIED
NIHDK078938
Subject Keywords:Bacteroides fragilis; Toll-like receptor 2colitis-associated colorectal cancer; inflammation; polysaccharide A
Issue or Number:6
PubMed Central ID:PMC6236802
Record Number:CaltechAUTHORS:20181115-081127417
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20181115-081127417
Official Citation:The Protective Role of Bacteroides fragilis in a Murine Model of Colitis-Associated Colorectal Cancer. Yun Kyung Lee, Parpi Mehrabian, Silva Boyajian, Wei-Li Wu, Jane Selicha, Steven Vonderfecht, Sarkis K. Mazmanian. mSphere Nov 2018, 3 (6) e00587-18; DOI: 10.1128/mSphere.00587-18
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90908
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:15 Nov 2018 16:51
Last Modified:24 Feb 2020 22:20

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