Virulence genes are a signature of the microbiome in the colorectal tumor microenvironment
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Abstract
Background: The human gut microbiome is associated with the development of colon cancer, and recent studies have found changes in the microbiome in cancer patients compared to healthy controls. Studying the microbial communities in the tumor microenvironment may shed light on the role of host–bacteria interactions in colorectal cancer. Here, we highlight the major shifts in the colorectal tumor microbiome relative to that of matched normal colon tissue from the same individual, allowing us to survey the microbial communities in the tumor microenvironment and providing intrinsic control for environmental and host genetic effects on the microbiome. Methods: We sequenced the microbiome in 44 primary tumor and 44 patient-matched normal colon tissue samples to determine differentially abundant microbial taxa These data were also used to functionally characterize the microbiome of the cancer and normal sample pairs and identify functional pathways enriched in the tumor-associated microbiota. Results: We find that tumors harbor distinct microbial communities compared to nearby healthy tissue. Our results show increased microbial diversity in the tumor microenvironment, with changes in the abundances of commensal and pathogenic bacterial taxa, including Fusobacterium and Providencia . While Fusobacterium has previously been implicated in colorectal cancer, Providencia is a novel tumor-associated agent which has not been identified in previous studies. Additionally, we identified a clear, significant enrichment of predicted virulence-associated genes in the colorectal cancer microenvironment, likely dependent upon the genomes of Fusobacterium and Providencia . Conclusions: This work identifies bacterial taxa significantly correlated with colorectal cancer, including a novel finding of an elevated abundance of Providencia in the tumor microenvironment. We also describe the predicted metabolic pathways and enzymes differentially present in the tumor-associated microbiome, and show an enrichment of virulence-associated bacterial genes in the tumor microenvironment. This predicted virulence enrichment supports the hypothesis that the microbiome plays an active role in colorectal cancer development and/or progression. Our results provide a starting point for future prognostic and therapeutic research with the potential to improve patient outcomes.
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F. nucleatum has been proved to be associated with CRC development and progression.
“which has been proved to be associated with CRC development and progression45,46.”
From A tumor microenvironment-specific gene expression signature predicts chemotherapy resistance in colorectal cancer patients (2021) · cites this paper as [46]
The Discussion (page unavailable) says there is a clear functional link between F. nucleatum and cancer development. The Background (page unavailable) describes Fusobacterium as thought to drive tumor formation and/or progression, but does not establish that F. nucleatum’s association with CRC progression has been proved. The claim overstates that part of the evidence. (LLM, conf=0.85)
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- Authors
- Burns, M. B., Lynch, J., Starr, T. K., Knights, D., & Blekhman, R.
- Affiliations
- University of Minnesota (US)
- Venue
- Genome Medicine
- Published
- 2015-06-24
- Volume
- 7
- Issue
- 1
- Pages
- 55-55
- ISSN
- 1756-994X (ISSN-L)
- PMC
- PMC4499914
- OpenAlex
- W1862711637
- Cited by
- 231
- References
- 9
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 21 · 2023: 25 · 2022: 16 · 2021: 23 · 2020: 31 · 2019: 25 · 2018: 17 · 2017: 23 · 2016: 9 · 2015: 6
- FWCI
- 7.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome Medicine (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Harvard University
- National Cancer Institute (R01CA134759)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Physical Sciences › Environmental Science › Ecology › Microbial Community Ecology and Physiology
- Keywords
- colorectal cancer, tumor microenvironment, gut microbiota, virulence genes, Fusobacterium, Providencia, host-bacteria interactions, microbial diversity, differentially abundant taxa, metabolic pathways
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