The Bacteroides fragilis Toxin Gene Is Prevalent in the Colon Mucosa of Colorectal Cancer Patients
Annemarie Boleij,Elizabeth M. Hechenbleikner,Andrew C. Goodwin,Ruchi Badani,Ellen M. Stein,Mark Lazarev,Brandon Ellis,Karen C. Carroll,Emilia Albesiano,Elizabeth C. Wick,Elizabeth A. Platz,Drew M. Pardoll,Cynthia L. Sears +12 more
TLDR
The results suggest that mucosal bft exposure is common and may be a risk factor for developing CRC.Abstract:
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.read more
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References
More filters
Journal ArticleDOI
Diversity of the human intestinal microbial flora.
Paul B. Eckburg,Elisabeth M. Bik,Charles N. Bernstein,Elizabeth Purdom,Les Dethlefsen,Michael Sargent,Steven R. Gill,Karen E. Nelson,David A. Relman,David A. Relman,David A. Relman +10 more
TL;DR: A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms, and significant intersubject variability and differences between stool and mucosa community composition were discovered.
Journal ArticleDOI
Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment.
TL;DR: The signal transducer and activator of transcription 3 (STAT3), which is a point of convergence for numerous oncogenic signalling pathways, is constitutively activated both in tumour cells and in immune cells in the tumour microenvironment.
Journal ArticleDOI
A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses
Shaoguang Wu,Ki Jong Rhee,Ki Jong Rhee,Ki Jong Rhee,Emilia Albesiano,Shervin Rabizadeh,Xinqun Wu,Hung-Rong Yen,Hung-Rong Yen,David L. Huso,Frederick L. Brancati,Elizabeth C. Wick,Florencia McAllister,Franck Housseau,Drew M. Pardoll,Cynthia L. Sears +15 more
TL;DR: Results show a Stat3- and TH17-dependent pathway for inflammation-induced cancer by a common human commensal bacterium, providing new mechanistic insight into human colon carcinogenesis.
Journal ArticleDOI
Mucosa-associated bacteria in the human gastrointestinal tract are uniformly distributed along the colon and differ from the community recovered from feces
Erwin G. Zoetendal,Terttu Vilpponen-Salmela,Kaouther Ben-Amor,Antoon D. L. Akkermans,Willem M. de Vos +4 more
TL;DR: The observed host-specific DGGE profiles of the mucosa-associated bacterial community in the colon support the hypothesis that host-related factors are involved in the determination of the GI tract microbial community.
Journal ArticleDOI
Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer.
TL;DR: The results suggest that the intestinal microbiota is associated with CRC risk and that intestinal lumen microflora potentially influence CRC risk via cometabolism or metabolic exchange with the host.
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