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Fusobacterium nucleatum Potentiates Intestinal Tumorigenesis and Modulates the Tumor-Immune Microenvironment
Open accessAbstract
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.
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“The gut microbiome has been shown to have multiple effects on tumor biology, such as the transformation process, tumor progression, and the response to anticancer therapies including immunotherapy (21-29).”
From The human tumor microbiome is composed of tumor type–specific intracellular bacteria (2020) · cites this paper as [22]
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“The activation of NF-kB promoted the transcription of pro-inflammatory cytokines such as TNF-α and IL-6, which may explain the accumulation of immunosuppressive myeloid cells in TME [59] (Fig. 2).”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [59]
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“Kostic et al. found a correlation between a high abundance of F. nucleatum and activated NF-κB in CRC.”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [59]
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Metadata
- Authors
- Kostic, A. D., Chun, E., Robertson, L., Glickman, J. N., Gallini, C. A., Michaud, M., Clancy, T. E., Chung, D. C., Lochhead, P., Hold, G. L., El-Omar, E. M., Brenner, D., Fuchs, C. S., Meyerson, M., & Garrett, W. S.
- Affiliations
- Broad Institute (US)
- Harvard University (US)
- Brigham and Women's Hospital (US)
- University of Aberdeen (GB)
- University of Michigan (US)
- Corresponding author
- Meyerson, Matthew
- Garrett, Wendy S.
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 14
- Issue
- 2
- Pages
- 207-215
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC3772512
- OpenAlex
- W2096139589
- Cited by
- 2,718
- References
- 43
- Citations by year
- 2026: 274 · 2025: 280 · 2024: 290 · 2023: 294 · 2022: 281 · 2021: 323 · 2020: 225 · 2019: 199 · 2018: 178 · 2017: 119 · 2016: 105 · 2015: 79 · 2014: 56 · 2013: 12
- FWCI
- 37.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Cancer Research Institute
- National Human Genome Research Institute (U54HG003067)
- National Cancer Institute (P50CA127003, RC2CA148317, R01CA154426)
- National Institute of Allergy and Infectious Diseases (K08AI078942)
- National Institute of Diabetes and Digestive and Kidney Diseases (K24DK098311, P30DK043351)
- National Institute of Environmental Health Sciences (T32ES016645)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
- Keywords
- Fusobacterium nucleatum, colorectal cancer, colorectal adenoma, gut microbiota, intestinal tumorigenesis, tumor microenvironment, tumor-infiltrating myeloid cells, pro-inflammatory microenvironment, ApcMin/+ mice, colonic neoplasia, inflammation-associated carcinogenesis
- MeSH terms
- Adenoma, Animals, Disease Models, Animal, Humans, Leukocytes, Colorectal Neoplasms, Cytokines, Fusobacterium nucleatum, Mice, Carcinogenesis
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