Fusobacterium nucleatum Potentiates Intestinal Tumorigenesis and Modulates the Tumor-Immune Microenvironment

Aleksandar D Kostic, Eunyoung Chun, Lauren Robertson, Jonathan N Glickman, Carey Ann Gallini, Monia Michaud, Thomas E Clancy, Daniel C Chung, Paul Lochhead, Georgina L Hold, Emad M El-Omar, Dean Brenner, Charles S Fuchs, Matthew Meyerson, Wendy S Garrett

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Abstract

Increasing evidence links the gut microbiota with colorectal cancer. Metagenomic analyses indicate that symbiotic Fusobacterium spp. are associated with human colorectal carcinoma, but whether this is an indirect or causal link remains unclear. We find that Fusobacterium spp. are enriched in human colonic adenomas relative to surrounding tissues and in stool samples from colorectal adenoma and carcinoma patients compared to healthy subjects. Additionally, in the Apc(Min/+) mouse model of intestinal tumorigenesis, Fusobacterium nucleatum increases tumor multiplicity and selectively recruits tumor-infiltrating myeloid cells, which can promote tumor progression. Tumors from Apc(Min/+) mice exposed to F. nucleatum exhibit a proinflammatory expression signature that is shared with human fusobacteria-positive colorectal carcinomas. However, unlike other bacteria linked to colorectal carcinoma, F. nucleatum does not exacerbate colitis, enteritis, or inflammation-associated intestinal carcinogenesis. Collectively, these data suggest that, through recruitment of tumor-infiltrating immune cells, fusobacteria generate a proinflammatory microenvironment that is conducive for colorectal neoplasia progression.
Original languageEnglish
Pages (from-to)207-215
Number of pages9
JournalCell Host & Microbe
Volume14
Issue number2
DOIs
Publication statusPublished - 14 Aug 2013

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Kostic, A. D., Chun, E., Robertson, L., Glickman, J. N., Gallini, C. A., Michaud, M., Clancy, T. E., Chung, D. C., Lochhead, P., Hold, G. L., El-Omar, E. M., Brenner, D., Fuchs, C. S., Meyerson, M., & Garrett, W. S. (2013). Fusobacterium nucleatum Potentiates Intestinal Tumorigenesis and Modulates the Tumor-Immune Microenvironment. Cell Host & Microbe, 14(2), 207-215. https://doi.org/10.1016/j.chom.2013.07.007