Abstract IA06: Colon cancer: Microbes and communities in microbiome translation

Abstract

Abstract Intensive efforts are under way to understand how the colon microbiome contributes to the pathogenesis of colorectal cancer (CRC) and to determine if and how the microbiome can be utilized in the prevention and/or therapy of CRC. Both single microbes and microbial communities are proposed as contributors to human CRC. Among single microbes, attention to date has focused on enterotoxigenic Bacteroides fragilis (ETBF), (pks+) Escherichia coli, and Fusobacterium spp., although other candidates are emerging. Among communities, one aspect has been the potential contribution of mucus-invasive, dense mucosal microbial communities termed biofilms to CRC disease pathogenesis. This talk will review select concepts within ETBF’s and biofilm contribution to colon carcinogenesis. While ETBF exposure is common, the risk of colon carcinogenesis in an individual is unknown but potentially influenced by colonization state, B. fragilis toxin isotype secreted by ETBF, colon site, and the underlying genomic state of the colonic epithelial cells. With respect to colon biofilms, about 50% of human sporadic colon cancer, particularly in the right colon, display polymicrobial biofilms with marked tumor infiltration with bacteria whereas ~15% of normal colonoscopy biopsies also reveal polymicrobial biofilms. These polymicrobial biofilms are typically composed of Bacteroidetes and Lachnospiraceae with a subset of tumors, but not biopsies, also displaying Fusobacterium. Further, samples from biofilm-positive human colon cancers induce assembly of biofilms in the distal germ-free mouse colon within a week following inoculation and are procarcinogenic (JCI 129:1699, 2019). One of the common hereditary human colon cancers (familial adenomatous polyposis; APC+/−) also displays biofilms but dominated by two bacteria, (pks+) E. coli and ETBF. A mouse model of (pks+) E. coli and ETBF cocolonization exhibited accelerated tumor formation and mortality when cocolonized with the cancer-inducing bacteria, potentially by fostering increased microbial adherence, IL-17, changes in gene expression, and enhanced colonic epithelial cell DNA damage (Science 2018;359:592-97). Current directions of translational research will be presented. Citation Format: Cynthia L. Sears. Colon cancer: Microbes and communities in microbiome translation [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr IA06.