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

Cell Host Microbe
Authors
Keywords
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.

Year of Publication
2013
Journal
Cell Host Microbe
Volume
14
Issue
2
Pages
207-15
Date Published
2013 Aug 14
ISSN
1934-6069
URL
DOI
10.1016/j.chom.2013.07.007
PubMed ID
23954159
PubMed Central ID
PMC3772512
Links
Grant list
R01CA154426 / 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