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Cell Host Microbe DOI:10.1016/j.chom.2013.07.007

Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment.

Publication TypeJournal Article
Year of Publication2013
AuthorsKostic, AD, Chun, E, Robertson, L, Glickman, JN, Gallini, CAnn, Michaud, M, Clancy, TE, Chung, DC, Lochhead, P, Hold, GL, El-Omar, EM, Brenner, D, Fuchs, CS, Meyerson, M, Garrett, WS
JournalCell Host Microbe
Date Published2013 Aug 14
KeywordsAdenoma, Animals, Carcinogenesis, Colorectal Neoplasms, Cytokines, Disease Models, Animal, Fusobacterium nucleatum, Humans, Leukocytes, Mice

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.


Alternate JournalCell Host Microbe
PubMed ID23954159
PubMed Central IDPMC3772512
Grant ListR01CA154426 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
RC2 CA148317 / CA / NCI NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
U54HG003067 / HG / NHGRI NIH HHS / United States
K08AI078942 / AI / NIAID NIH HHS / United States
K24 DK098311 / DK / NIDDK NIH HHS / United States
K08 AI078942 / AI / NIAID NIH HHS / United States
P50CA127003 / CA / NCI NIH HHS / United States
R01 CA154426 / CA / NCI NIH HHS / United States
RC2CA148317 / CA / NCI NIH HHS / United States
T32 ES016645 / ES / NIEHS NIH HHS / United States
P50 CA127003 / CA / NCI NIH HHS / United States
CAF/10/15 / / Chief Scientist Office / United Kingdom