title: Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment.
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.
authors: Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors: Aleksandar D
authors: AD
authors: Kostic
authors: Eunyoung
authors: E
authors: Chun
authors: Lauren
authors: L
authors: Robertson
authors: Jonathan N
authors: JN
authors: Glickman
authors: Carey Ann
authors: CA
authors: Gallini
authors: Monia
authors: M
authors: Michaud
authors: Thomas E
authors: TE
authors: Clancy
authors: Daniel C
authors: DC
authors: Chung
authors: Paul
authors: P
authors: Lochhead
authors: Georgina L
authors: GL
authors: Hold
authors: Emad M
authors: EM
authors: El-Omar
authors: Dean
authors: D
authors: Brenner
authors: Charles S
authors: CS
authors: Fuchs
authors: Matthew
authors: M
authors: Meyerson
authors: Wendy S
authors: WS
authors: Garrett
mesh_terms: D000236:Adenoma / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D000818:Animals; D063646:Carcinogenesis / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D016967:Fusobacterium nucleatum / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D051379:Mice
chemical_list: D016207:Cytokines
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