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

Research output: Contribution to journalArticle

570 Citations (Scopus)

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

Fingerprint

Fusobacterium nucleatum
Tumor Microenvironment
Carcinogenesis
Colorectal Neoplasms
Fusobacteria
Fusobacterium
Neoplasms
Adenoma
Metagenomics
Enteritis
Myeloid Cells
Colitis
Healthy Volunteers
Inflammation
Bacteria

Cite this

Kostic, A. D., Chun, E., Robertson, L., Glickman, J. N., Gallini, C. A., Michaud, 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

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

In: Cell Host & Microbe, Vol. 14, No. 2, 14.08.2013, p. 207-215.

Research output: Contribution to journalArticle

Kostic, AD, Chun, E, Robertson, L, Glickman, JN, Gallini, CA, Michaud, M, Clancy, TE, Chung, DC, Lochhead, P, Hold, GL, El-Omar, EM, Brenner, D, Fuchs, CS, Meyerson, M & Garrett, WS 2013, 'Fusobacterium nucleatum Potentiates Intestinal Tumorigenesis and Modulates the Tumor-Immune Microenvironment', Cell Host & Microbe, vol. 14, no. 2, pp. 207-215. https://doi.org/10.1016/j.chom.2013.07.007
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. / Fusobacterium nucleatum Potentiates Intestinal Tumorigenesis and Modulates the Tumor-Immune Microenvironment. In: Cell Host & Microbe. 2013 ; Vol. 14, No. 2. pp. 207-215.
@article{adbbec7edf274b0fb73d9f2e4845d097,
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.",
author = "Kostic, {Aleksandar D} and Eunyoung Chun and Lauren Robertson and Glickman, {Jonathan N} and Gallini, {Carey Ann} and Monia Michaud and Clancy, {Thomas E} and Chung, {Daniel C} and Paul Lochhead and Hold, {Georgina L} and El-Omar, {Emad M} and Dean Brenner and Fuchs, {Charles S} and Matthew Meyerson and Garrett, {Wendy S}",
note = "Copyright {\circledC} 2013 Elsevier Inc. All rights reserved.",
year = "2013",
month = "8",
day = "14",
doi = "10.1016/j.chom.2013.07.007",
language = "English",
volume = "14",
pages = "207--215",
journal = "Cell Host & Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Fusobacterium nucleatum Potentiates Intestinal Tumorigenesis and Modulates the Tumor-Immune Microenvironment

AU - Kostic, Aleksandar D

AU - Chun, Eunyoung

AU - Robertson, Lauren

AU - Glickman, Jonathan N

AU - Gallini, Carey Ann

AU - Michaud, Monia

AU - Clancy, Thomas E

AU - Chung, Daniel C

AU - Lochhead, Paul

AU - Hold, Georgina L

AU - El-Omar, Emad M

AU - Brenner, Dean

AU - Fuchs, Charles S

AU - Meyerson, Matthew

AU - Garrett, Wendy S

N1 - Copyright © 2013 Elsevier Inc. All rights reserved.

PY - 2013/8/14

Y1 - 2013/8/14

N2 - 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.

AB - 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.

U2 - 10.1016/j.chom.2013.07.007

DO - 10.1016/j.chom.2013.07.007

M3 - Article

VL - 14

SP - 207

EP - 215

JO - Cell Host & Microbe

JF - Cell Host & Microbe

SN - 1931-3128

IS - 2

ER -