Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor immune microenvironment

By A. Kostic, Eunyoung Chun, Lauren Robertson, J. Glickman, C. Gallini, M. Michaud, T. Clancy, D. Chung, P. Lochhead, G. Hold and 5 more. Cell Host and Microbe, 2013

2,449 citations recorded by the source corpus.

SUMMARY Increasing evidence links the gut microbiota with colorectal cancer. Metagenomic analyses indicate that commensal 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 pro-inflammatory 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 pro-inflammatory microenvironment that is conducive for colorectal neoplasia progression.

Subfields: Molecular Biology, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/f5b6d67e05a413f91983c32d9dd0b7ae246e0ce8

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In Molecular Biology

1. Curtis Huttenhower
2. Eric A. Franzosa
3. W. Garrett
4. Dirk Gevers
5. B. Goodman
6. H. Gardner
7. Ramnik J. Xavier
8. Eric S. Lander

In Neurology

1. Curtis Huttenhower
2. Dirk Gevers
3. W. Garrett

In Physiology

1. Curtis Huttenhower
2. Dirk Gevers
3. A. Alimonti
4. Henry J. Haiser
5. C. Mantzoros
6. Herbert W. Virgin
7. J. Kohli
8. E. Zagato

Citations in the corpus

• The human microbiome (2017, background): “One study found that introducing Fusobacterium into mice that develop intestinal tumors accelerated tumor development and induced a proinflammatory response [22].”
• The gut microbiome in health and in disease (2015, background): “In this section, we highlight a few of the recent findings on the role of the microbiota in particular diseases or conditions, but we cannot touch on all of the emerging findings in a multitude of other diseases both inside and outside the gut, including but not limited to rheumatoid arthritis [25],”
• Obesity and cancer risk: Emerging biological mechanisms and perspectives. (2019, background): “Adenomatous Polyposis Coli (APC) deficient mice fed with Fusobacteria exhibited higher number of tumors and a more rapid intestinal tumor progression compared to controls fed with Streptococci [7,204,205].”
• Role of the Microbiota in Immunity and inflammation (2014, background): “Bacteria of the phylum Fusobacteria are also found at a high frequency residing within the tumor tissue and are important in inducing the traffic of tumor-promoting myeloid cells (Kostic et al., 2012, 2013; Rubinstein et al., 2013).”
• The microbiome and cancer (2018, background): “Fusobacterium Increase in IL-6, IL-8, IL-18 and NF-κB signalling Kostic et al (2013) [46] Rubinstein et al (2013) [52] Helicobacter Increase in IL-1B, IL-8 and NF-κB signalling through CagA Peek and Blaser (2002) [58]”
• Cellular Senescence: Aging, Cancer, and Injury. (2019, background): “An intriguing aspect of the role of MDSCs in cancer is that their abundance in biopsies has prognostic relevance in cancer patients (92).”
• Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin (2013, background): “In this issue of Cell Host and Microbe, Kostic et al showed that Fn generates a proinflammatory microenvironment that is conducive for colorectal neoplasia progression (Kostic et al., 2013).”
• Natural history of the infant gut microbiome and impact of antibiotic treatments on strain-level diversity and stability (2015, background): “These studies have largely focused on characterizing healthy adults (1) and finding commonalities among patients suffering from diseases such as inflammatory bowel disease (2, 3), type 2 diabetes (4), obesity (5–9), metabolic disorders (10–15), colorectal cancer (16, 17), liver cirrhosis (18, 19), r”