title: The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients.
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.
authors.affiliation: Department of Medicine.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Boleij
authors.affiliation: Department of Surgery.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Hechenbleikner
authors.affiliation: Department of Medicine.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Goodwin
authors.affiliation: Department of Oncology.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Badani
authors.affiliation: Department of Medicine.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Stein
authors.affiliation: Department of Medicine.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lazarev
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine.
authors.forename: Brandon
authors.initials: B
authors.lastname: Ellis
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine.
authors.forename: Karen C
authors.initials: KC
authors.lastname: Carroll
authors.affiliation: Department of Medicine.
authors.forename: Emilia
authors.initials: E
authors.lastname: Albesiano
authors.affiliation: Department of Surgery.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Wick
authors.affiliation: Department of Oncology Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
authors.affiliation: Department of Medicine Department of Oncology Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Drew M
authors.initials: DM
authors.lastname: Pardoll
authors.affiliation: Department of Medicine Department of Oncology Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Sears
mesh_terms: D000368:Aged; D001427:Bacterial Toxins / Q000235:genetics*; D001441:Bacteroides fragilis / Q000235:genetics*; D003106:Colon / Q000382:microbiology / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000382:microbiology / Q000473:pathology*; D004269:DNA, Bacterial / Q000032:analysis* / Q000235:genetics; D005260:Female; D005798:Genes, Bacterial; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology*; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics*; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D001427:Bacterial Toxins; D004269:DNA, Bacterial; C405031:Bacteroides fragilis toxin; D008666:Metalloendopeptidases
keywords: Bacteroides fragilis toxin; colorectal cancer; enterotoxigenic Bacteroides fragilis; mucosal microbiota