Grant Number:	1R01CA151393-01 Interpret this number
Primary Investigator:	Sears, Cynthia
Organization:	Johns Hopkins University
Project Title:	Enterotoxigenic Bacteroides Fragilis: a Bacterial Promoter of Colon Oncogenesis
Fiscal Year:	2010

DESCRIPTION (provided by applicant): We have identified a human colon anaerobic bacterium, enterotoxigenic Bacteroides fragilis (ETBF), as a candidate etiologic agent for colon cancer and our murine models of ETBF colonization delineate a potential procarcinogenic immune pathway that ETBF induce. Just as the understanding of peptic ulcer disease and ensuing stomach cancer was transformed by the discovery of H. pylori, we hypothesize that ETBF, by secreting the potent B. fragilis toxin (BFT), precipitate procarcinogenic mucosal immune responses, thereby promoting formation of colon cancer. Our model does not propose to alter existing mutational paradigms of colon cancer but rather proposes that ETBF colonization is an integral mechanism accounting for the accumulation of genetic mutations necessary for colon carcinogenesis. This proposal will study the relationship between colon colonization by ETBF in humans, specific colon immune responses and, ultimately, colon cancer. Defining a microbial etiology for colon cancer has key implications as colon cancer is a major public health problem being the second leading cause of cancer death in the United States in women and men. A significant correlation between any two of the studied variables - ETBF colonization, colon immune responses and colon cancer -- will substantively alter current paradigms for the pathogenesis, prevention and therapy of colon cancer. PUBLIC HEALTH RELEVANCE: Colon cancer is the second leading cause of cancer death for women and men. Current approaches to prevention of colon cancer are cumbersome and underutilized due to their expense and inconvenience. This project proposes that colon cancer is triggered by a common stool bacterium called enterotoxigenic Bacteroides fragilis (ETBF) and will test whether detection of ETBF and/or the colon immune response to ETBF provide new, easier approaches to the prevention of the morbidity and mortality due to colon cancer.




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Source: Msystems, 2020-01-14 00:00:00.0; 5(1), .
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PMID: 31937674
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Human colon mucosal biofilms from healthy or colon cancer hosts are carcinogenic.
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Authors: Dejea C.M. , Fathi P. , Craig J.M. , Boleij A. , Taddese R. , Geis A.L. , Wu X. , DeStefano Shields C.E. , Hechenbleikner E.M. , Huso D.L. , et al. .
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Sam68/KHDRBS1 is critical for colon tumorigenesis by regulating genotoxic stress-induced NF-κB activation.
Authors: Fu K. , Sun X. , Wier E.M. , Hodgson A. , Liu Y. , Sears C.L. , Wan F. .
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Redundant Innate and Adaptive Sources of IL17 Production Drive Colon Tumorigenesis.
Authors: Housseau F. , Wu S. , Wick E.C. , Fan H. , Wu X. , Llosa N.J. , Smith K.N. , Tam A. , Ganguly S. , Wanyiri J.W. , et al. .
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Do biofilms confer a pro-carcinogenic state?
Authors: Dejea C.M. , Sears C.L. .
Source: Gut Microbes, 2016; 7(1), p. 54-7.
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The intestinal microbiome and health.
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Fecal detection of enterotoxigenic Bacteroides fragilis.
Authors: Chen L.A. , Van Meerbeke S. , Albesiano E. , Goodwin A. , Wu S. , Yu H. , Carroll K. , Sears C. .
Source: European Journal Of Clinical Microbiology & Infectious Diseases : Official Publication Of The European Society Of Clinical Microbiology, 2015 Sep; 34(9), p. 1871-7.
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Metabolism links bacterial biofilms and colon carcinogenesis.
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The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients.
Authors: Boleij A. , Hechenbleikner E.M. , Goodwin A.C. , Badani R. , Stein E.M. , Lazarev M.G. , Ellis B. , Carroll K.C. , Albesiano E. , Wick E.C. , et al. .
Source: Clinical Infectious Diseases : An Official Publication Of The Infectious Diseases Society Of America, 2015-01-15 00:00:00.0; 60(2), p. 208-15.
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Bacteroides fragilis subverts mucosal biology: from symbiont to colon carcinogenesis.
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Bacterial oncogenesis in the colon.
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Shift from pStat6 to pStat3 predominance is associated with inflammatory bowel disease-associated dysplasia.
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