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The Bacteroides fragilis Toxin Gene Is Prevalent in the Colon Mucosa of Colorectal Cancer Patients

作者: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 · 发表于:Clinical Infectious Diseases · 年份:2014 · DOI:10.1093/cid/ciu787 · 被引用次数:635 · 研究领域:Bacterial Identification and Susceptibility Testing、Clostridium difficile and Clostridium perfringens research、Gut microbiota and health

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, wherea...