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.
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 neoplasiapatients (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: Paul B Eckburg; Elisabeth M Bik; Charles N Bernstein; Elizabeth Purdom; Les Dethlefsen; Michael Sargent; Steven R Gill; Karen E Nelson; David A Relman Journal: Science Date: 2005-04-14 Impact factor: 47.728
Authors: N Ulger Toprak; A Yagci; B M Gulluoglu; M L Akin; P Demirkalem; T Celenk; G Soyletir Journal: Clin Microbiol Infect Date: 2006-08 Impact factor: 8.067
Authors: L L Myers; D S Shoop; L L Stackhouse; F S Newman; R J Flaherty; G W Letson; R B Sack Journal: J Clin Microbiol Date: 1987-12 Impact factor: 5.948
Authors: Aaron L Hecht; Benjamin W Casterline; Zachary M Earley; Young Ah Goo; David R Goodlett; Juliane Bubeck Wardenburg Journal: EMBO Rep Date: 2016-07-18 Impact factor: 8.807
Authors: Vanessa L Hale; Patricio Jeraldo; Michael Mundy; Janet Yao; Gary Keeney; Nancy Scott; E Heidi Cheek; Jennifer Davidson; Megan Greene; Christine Martinez; John Lehman; Chandra Pettry; Erica Reed; Kelly Lyke; Bryan A White; Christian Diener; Osbaldo Resendis-Antonio; Jaime Gransee; Tumpa Dutta; Xuan-Mai Petterson; Lisa Boardman; David Larson; Heidi Nelson; Nicholas Chia Journal: Methods Date: 2018-04-26 Impact factor: 3.608
Authors: Matthew Silbergleit; Adrian A Vasquez; Carol J Miller; Jun Sun; Ikuko Kato Journal: Prog Mol Biol Transl Sci Date: 2020-04-09 Impact factor: 3.622
Authors: Christina E DeStefano Shields; Sara W Van Meerbeke; Franck Housseau; Hao Wang; David L Huso; Robert A Casero; Heather M O'Hagan; Cynthia L Sears Journal: J Infect Dis Date: 2016-02-21 Impact factor: 5.226
Authors: Liam Chung; Erik Thiele Orberg; Abby L Geis; June L Chan; Kai Fu; Christina E DeStefano Shields; Christine M Dejea; Payam Fathi; Jie Chen; Benjamin B Finard; Ada J Tam; Florencia McAllister; Hongni Fan; Xinqun Wu; Sudipto Ganguly; Andriana Lebid; Paul Metz; Sara W Van Meerbeke; David L Huso; Elizabeth C Wick; Drew M Pardoll; Fengyi Wan; Shaoguang Wu; Cynthia L Sears; Franck Housseau Journal: Cell Host Microbe Date: 2018-02-01 Impact factor: 21.023