Abstract A09: Understanding the role of colorectal cancer-associated microbes in colorectal cancer

Abstract

Accumulating evidence suggests that dysbiosis, a state of pathologic imbalance in the human gut microbiome, is present in patients suffering from colorectal cancer (CRC). Several microbiome studies identified specific bacteria that are associated with CRC, among which Fusobacteria were shown to directly interact with cancer or immune cells of their host. However, only a limited number of CRC-associated microbes have been studied for host-microbial interactions; hence, the role of bacteria in the etiology of the disease remains unknown. Accordingly, our work aims at the development of a methodologic workflow for studying CRC-associated bacteria and their role in colon cancer tumor initiation and progression. In a first step, we identified CRC-associated bacteria that are enriched at the tumor site of CRC patients. Therefore, we used publicly available datasets and an in-house patient sample collection. Then, we predicted and optimized bacterial growth in silico by using a genome-scale metabolic reconstruction model combined with a constraint-based modeling approach. Finally, we implemented CRC-associated bacteria together with established primary CRC patient cultures into the microfluidics-based human-microbial crosstalk model (HuMiX). Our workflow allowed to analyze host-microbial interaction mechanisms of CRC-associated bacteria on a transcriptomic, proteomic, and metabolomic level. Citation Format: Dominik Ternes, Martine Schmitz, Léa Grandmougin, Mina Tsenkova, Eric Koncina, Aurélien Ginolhac, Jessica Karta, Diana Kuhn, Javier Ramiro Garcia, Kacy Greenhalgh, Paul Wilmes, Elisabeth Letellier, Serge Haan. Understanding the role of colorectal cancer-associated microbes 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 A09.