Abstract IA07: The plasticity of the intestinal microbiota in colorectal cancer

Abstract

Abstract Gene-environment interaction plays a key role in disease susceptibility, including colorectal cancer. Microbiota, particularly the intestinal bacteriome, plays a central role in host physiology, and the composition and activity of this consortium of microorganisms is directly influenced by known cancer risk factors such as lifestyle, diet, and inflammation. Accumulating evidence points to a role of microbiota in carcinogenesis. The mechanism by which microbiota impacts on cancer development is still unclear, but alteration in genomic stability (genetics and epigenetics) is considered a converging point. Inflammation represents a powerful condition by which microbial composition and biologic activities are altered. Using gnotobiotic technology, microbial genetic manipulation, genetically engineered mice (Apcmin/+; Il10-/-), and microbial genomics, we investigated the role of specific bacterial or consortium of bacteria in the development of colitis-associated colorectal cancer. In this lecture, I will provide evidence that specific microbial genotoxic activities originating from various strains such as Escherichia coli and Campylobacter jejuni promote development of CRC. For example, the presence of DNA-damaging toxins such as colibactin from adherent invasive Escherichia coli or cytolethal distending toxins (cdt) from Campylobacter jejuni is critical for development of colorectal cancer. I will address the relationship between inflammation and bacteria-induced carcinogenesis by studying the effect of neutralizing TNFa antibody, a biologic used to manage intestinal bowel disease, on microbial community activity. These studies represent the first step toward understanding mechanisms by which microbiota influences development of colorectal cancer, and shed light on how alteration of environmental factors modulates microbial carcinogenic potential. Citation Format: Ye Yang, Raad Gharaibeh, Christian Jobin. The plasticity of the intestinal microbiota in colorectal cancer [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 IA07.