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

• Published in: Cell host & microbe Vol. 14; no. 2; pp. 207 - 215
• Main Authors: Kostic, Aleksandar D., Chun, Eunyoung, Robertson, Lauren, Glickman, Jonathan N., Gallini, Carey Ann, Michaud, Monia, Clancy, Thomas E., Chung, Daniel C., Lochhead, Paul, Hold, Georgina L., El-Omar, Emad M., Brenner, Dean, Fuchs, Charles S., Meyerson, Matthew, Garrett, Wendy S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.08.2013
• Subjects: adenoma; Adenoma - immunology; Adenoma - microbiology; Adenoma - pathology; animal models; Animals; bacteria; carcinogenesis; Carcinogenesis - immunology; carcinoma; colitis; colorectal neoplasms; Colorectal Neoplasms - immunology; Colorectal Neoplasms - microbiology; Colorectal Neoplasms - pathology; Cytokines - biosynthesis; Disease Models, Animal; enteritis; feces; Fusobacterium nucleatum; Fusobacterium nucleatum - immunology; Fusobacterium nucleatum - pathogenicity; Humans; intestinal microorganisms; Leukocytes - immunology; metagenomics; Mice; patients
• ISSN: 1931-3128; 1934-6069; 1934-6069
• DOI: 10.1016/j.chom.2013.07.007

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 ApcMin/+ mouse model of intestinal tumorigenesis, Fusobacterium nucleatum increases tumor multiplicity and selectively recruits tumor-infiltrating myeloid cells, which can promote tumor progression. Tumors from ApcMin/+ 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. •Fusobacterium is enriched in human adenomas, suggesting an early role in tumorigenesis•Fusobacterium nucleatum accelerates tumorigenesis in ApcMin/+ mice•F. nucleatum drives myeloid cell infiltration in intestinal tumors•Fusobacterium is associated with a proinflammatory signature in mouse and human tumors