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Quantitative Profiling of Colorectal Cancer-Associated Bacteria Reveals Associations between Fusobacterium spp., Enterotoxigenic Bacteroides fragilis (ETBF) and Clinicopathological Features of Colorectal Cancer
Open accessAbstract
Various studies have presented clinical or in vitro evidence linking bacteria to colorectal cancer, but these bacteria have not previously been concurrently quantified by qPCR in a single cohort. We quantify these bacteria (Fusobacterium spp., Streptococcus gallolyticus, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis (ETBF), Enteropathogenic Escherichia coli (EPEC), and afaC- or pks-positive E. coli) in paired tumour and normal tissue samples from 55 colorectal cancer patients. We further investigate the relationship between a) the presence and b) the level of colonisation of each bacterial species with site and stage of disease, age, gender, ethnicity and MSI-status. With the exception of S. gallolyticus, we detected all bacteria profiled here in both tumour and normal samples at varying frequencies. ETBF (FDR = 0.001 and 0.002 for normal and tumour samples) and afaC-positive E. coli (FDR = 0.03, normal samples) were significantly enriched in the colon compared to the rectum. ETBF (FDR = 0.04 and 0.002 for normal and tumour samples, respectively) and Fusobacterium spp. (FDR = 0.03 tumour samples) levels were significantly higher in late stage (III/IV) colorectal cancers. Fusobacterium was by far the most common bacteria detected, occurring in 82% and 81% of paired tumour and normal samples. Fusobacterium was also the only bacterium that was significantly higher in tumour compared to normal samples (p = 6e-5). We also identified significant associations between high-level colonisation by Fusobacterium and MSI-H (FDR = 0.05), age (FDR = 0.03) or pks-positive E. coli (FDR = 0.01). Furthermore, we exclusively identified atypical EPEC in our cohort, which has not been previously reported in association with colorectal cancer. By quantifying colorectal cancer-associated bacteria across a single cohort, we uncovered inter- and intra-individual patterns of colonization not previously recognized, as well as important associations with clinicopathological features, especially in the case of Fusobacterium and ETBF.
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“Among them, 2 found significant enrichment of ETBF in tumor tissues compared to tissues from controls or adjacent normal tissues40, 43.”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [43]
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Metadata
- Authors
- Viljoen, K. S., Dakshinamurthy, A., Goldberg, P., & Blackburn, J. M.
- Affiliations
- University of Cape Town (ZA)
- Groote Schuur Hospital (ZA)
- Corresponding author
- Blackburn, Jonathan M.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-03-09
- Volume
- 10
- Issue
- 3
- Pages
- e0119462
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4353626
- OpenAlex
- W2086248022
- Cited by
- 256
- References
- 74
- Citations by year
- 2026: 14 · 2025: 26 · 2024: 25 · 2023: 32 · 2022: 29 · 2021: 34 · 2020: 21 · 2019: 23 · 2018: 21 · 2017: 16 · 2016: 12 · 2015: 1
- FWCI
- 7.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Open University of Cape Town (University of Cape Town) (submittedVersion, cc-by)
- Funders
- National Research Foundation
- Cancer Association of South Africa
- Deutscher Akademischer Austauschdienst
- Harry Crossley Foundation
- University of Cape Town
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- colorectal cancer, Fusobacterium, enterotoxigenic Bacteroides fragilis, Streptococcus bovis, Enterococcus faecalis, enteropathogenic Escherichia coli, tumor microbiome, tumor stage, microsatellite instability, clinicopathological features
- MeSH terms
- Adenocarcinoma, Adult, Bacterial Infections, Bacteroides fragilis, Colon, Female, Fusobacterium, Genes, Bacterial, Humans, Male, Middle Aged, Neoplasm Staging, Rectum, Colorectal Neoplasms, Case-Control Studies, Enteropathogenic Escherichia coli, Bacterial Load
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