The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients
Open accessAbstract
BACKGROUND: Enterotoxigenic Bacteroides fragilis (ETBF) produces the Bacteroides fragilis toxin, which has been associated with acute diarrheal disease, inflammatory bowel disease, and colorectal cancer (CRC). ETBF induces colon carcinogenesis in experimental models. Previous human studies have demonstrated frequent asymptomatic fecal colonization with ETBF, but no study has investigated mucosal colonization that is expected to impact colon carcinogenesis. METHODS: We compared the presence of the bft gene in mucosal samples from colorectal neoplasia patients (cases, n = 49) to a control group undergoing outpatient colonoscopy for CRC screening or diagnostic workup (controls, n = 49). Single bacterial colonies isolated anaerobically from mucosal colon tissue were tested for the bft gene with touch-down polymerase chain reaction. RESULTS: The mucosa of cases was significantly more often bft-positive on left (85.7%) and right (91.7%) tumor and/or paired normal tissues compared with left and right control biopsies (53.1%; P = .033 and 55.5%; P = .04, respectively). Detection of bft was concordant in most paired mucosal samples from individual cases or controls (75% cases; 67% controls). There was a trend toward increased bft positivity in mucosa from late- vs early-stage CRC patients (100% vs 72.7%, respectively; P = .093). In contrast to ETBF diarrheal disease where bft-1 detection dominates, bft-2 was the most frequent toxin isotype identified in both cases and controls, whereas multiple bft isotypes were detected more frequently in cases (P ≤ .02). CONCLUSIONS: The bft gene is associated with colorectal neoplasia, especially in late-stage CRC. Our results suggest that mucosal bft exposure is common and may be a risk factor for developing CRC.
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Two studies found significant enrichment of enterotoxigenic Bacteroides fragilis in tumor tissues compared with controls or adjacent normal tissues.
“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 [40]
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- Authors
- Boleij, A., Hechenbleikner, E. M., Goodwin, A. C., Badani, R., Stein, E. M., Lazarev, M. G., Ellis, B., Carroll, K. C., Albesiano, E., Wick, E. C., Platz, E. A., Pardoll, D. M., & Sears, C. L.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Sears, Cynthia L.
- ORCID
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-10-09
- Volume
- 60
- Issue
- 2
- Pages
- 208-215
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC4351371
- OpenAlex
- W2154075765
- Cited by
- 625
- References
- 41
- Citations by year
- 2026: 58 · 2025: 62 · 2024: 75 · 2023: 72 · 2022: 73 · 2021: 65 · 2020: 54 · 2019: 48 · 2018: 47 · 2017: 31 · 2016: 26 · 2015: 13
- FWCI
- 16.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Infectious Diseases (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (825.11.031)
- National Institutes of Health
- National Cancer Institute (T32CA126607, R01CA151393, P50CA062924, P30CA021765)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK087856)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Keywords
- Bacteroides fragilis, enterotoxigenic Bacteroides fragilis, Bacteroides fragilis toxin, colorectal cancer, colonic mucosa, mucosal colonization, colon carcinogenesis, tumor stage, colorectal neoplasia
- MeSH terms
- Aged, Bacterial Toxins, Bacteroides fragilis, Colon, DNA, Bacterial, Female, Genes, Bacterial, Humans, Intestinal Mucosa, Male, Metalloendopeptidases, Middle Aged, Risk Factors, Colorectal Neoplasms
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