The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
A Gnotobiotic Mouse Model Demonstrates That Dietary Fiber Protects against Colorectal Tumorigenesis in a Microbiota- and Butyrate-Dependent Manner
Open accessAbstract
Whether dietary fiber protects against colorectal cancer is controversial because of conflicting results from human epidemiologic studies. However, these studies and mouse models of colorectal cancer have not controlled the composition of gut microbiota, which ferment fiber into short-chain fatty acids such as butyrate. Butyrate is noteworthy because it has energetic and epigenetic functions in colonocytes and tumor-suppressive properties in colorectal cancer cell lines. We used gnotobiotic mouse models colonized with wild-type or mutant strains of a butyrate-producing bacterium to demonstrate that fiber does have a potent tumor-suppressive effect but in a microbiota- and butyrate-dependent manner. Furthermore, due to the Warburg effect, butyrate was metabolized less in tumors where it accumulated and functioned as a histone deacetylase (HDAC) inhibitor to stimulate histone acetylation and affect apoptosis and cell proliferation. To support the relevance of this mechanism in human cancer, we demonstrate that butyrate and histone-acetylation levels are elevated in colorectal adenocarcinomas compared with normal colonic tissues. Significance: These results, which link diet and microbiota to a tumor-suppressive metabolite, provide insight into conflicting epidemiologic findings and suggest that probiotic/prebiotic strategies can modulate an endogenous HDAC inhibitor for anticancer chemoprevention without the adverse effects associated with synthetic HDAC inhibitors used in chemotherapy. Cancer Discov; 4(12); 1387–97. ©2014 AACR. See related commentary by Sebastián and Mostoslavsky, p. 1368 This article is highlighted in the In This Issue feature, p. 1355
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Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
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“Our data also support a molecular mechanism where microbial fermentation of fiber yields butyrate, which serves as the preferred energy source of normal colonocytes and supports homeostasis (11,25) but accumulates in cancerous colonocytes due to the Warburg effect and functions as an HDAC inhibitor to inhibit cell pro…”
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Cited by
Gut microbiota, metabolites and host immunity
Rooks, M. G., & Garrett, W. S. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.42 · Cited by 3,409
Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer
Mármol, I., Sánchez-de-Diego, C., Pradilla Dieste, A., Cerrada, E., & Rodriguez Yoldi, M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18010197 · Cited by 1,525
Garrett, W. S. (2015) · Science · doi:10.1126/science.aaa4972 · Cited by 1,404
Gut microbial metabolites as multi-kingdom intermediates
Krautkramer, K. A., Fan, J., & Bäckhed, F. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-020-0438-4 · Cited by 1,398
Diet, microorganisms and their metabolites, and colon cancer
O'Keefe, S. J. D. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.165 · Cited by 1,100
Metadata
- Authors
- Donohoe, D. R., Holley, D., Collins, L. B., Montgomery, S. A., Whitmore, A. C., Hillhouse, A., Curry, K. P., Renner, S. W., Greenwalt, A., Ryan, E. P., Godfrey, V., Heise, M. T., Threadgill, D. S., Han, A., Swenberg, J. A., Threadgill, D. W., & Bultman, S. J.
- Venue
- Cancer Discovery
- Published
- 2014-12-01
- Volume
- 4
- Issue
- 12
- Pages
- 1387-1397
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2048994952
- Cited by
- 474
- References
- 14
- FWCI
- 10.59
- Type
- journal article
- Language
- en
- Open access
- green
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- Donohoe, D. R., Holley, D., Collins, L. B., Montgomery, S. A., Whitmore, A. C., Hillhouse, A., Curry, K. P., Renner, S. W., Greenwalt, A., Ryan, E. P., Godfrey, V., Heise, M. T., Threadgill, D. S., Han, A., Swenberg, J. A., Threadgill, D. W., & Bultman, S. J. (2014). A Gnotobiotic Mouse Model Demonstrates That Dietary Fiber Protects against Colorectal Tumorigenesis in a Microbiota- and Butyrate-Dependent Manner. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-14-0501
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
