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 Stein, Mark Lazarev, Brandon Ellis, Karen C Carroll, Emilia Albesiano, Elizabeth C. Wick, Elizabeth A Platz, Andrew Mark Pardoll, Cynthia Louise Sears

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)208-215
Number of pages8
JournalClinical Infectious Diseases
Volume60
Issue number2
DOIs
StatePublished - Jan 15 2015

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Bacteroides fragilis
Colorectal Neoplasms
Colon
Mucous Membrane
Genes
Carcinogenesis
Neoplasms
Touch
Acute Disease
Colonoscopy
Inflammatory Bowel Diseases
Early Detection of Cancer
Theoretical Models
Outpatients
Bacteroides fragilis toxin
Biopsy
Polymerase Chain Reaction
Control Groups

Keywords

  • Bacteroides fragilis toxin
  • colorectal cancer
  • enterotoxigenic Bacteroides fragilis
  • mucosal microbiota

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)

Cite this

The bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients. / Boleij, Annemarie; Hechenbleikner, Elizabeth M.; Goodwin, Andrew C.; Badani, Ruchi; Stein, Ellen; Lazarev, Mark; Ellis, Brandon; Carroll, Karen C; Albesiano, Emilia; Wick, Elizabeth C.; Platz, Elizabeth A; Pardoll, Andrew Mark; Sears, Cynthia Louise.

In: Clinical Infectious Diseases, Vol. 60, No. 2, 15.01.2015, p. 208-215.

Research output: Contribution to journalArticle

Boleij, Annemarie ; Hechenbleikner, Elizabeth M. ; Goodwin, Andrew C. ; Badani, Ruchi ; Stein, Ellen ; Lazarev, Mark ; Ellis, Brandon ; Carroll, Karen C ; Albesiano, Emilia ; Wick, Elizabeth C. ; Platz, Elizabeth A ; Pardoll, Andrew Mark ; Sears, Cynthia Louise. / The bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients. In: Clinical Infectious Diseases. 2015 ; Vol. 60, No. 2. pp. 208-215.
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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.",
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AU - Boleij, Annemarie

AU - Hechenbleikner, Elizabeth M.

AU - Goodwin, Andrew C.

AU - Badani, Ruchi

AU - Stein, Ellen

AU - Lazarev, Mark

AU - Ellis, Brandon

AU - Carroll, Karen C

AU - Albesiano, Emilia

AU - Wick, Elizabeth C.

AU - Platz, Elizabeth A

AU - Pardoll, Andrew Mark

AU - Sears, Cynthia Louise

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N2 - 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.

AB - 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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