Abstract 5078: Metaproteomic analysis of IBD associated colorectal cancer

Abstract Inflammatory bowel disease (IBD) increases the risk of developing colorectal cancer by 60%. The composition of gut flora and its interaction with mucosal cells plays a key role in the development of IBD and colorectal cancer. However, the actual cause-effect relationship between dysbiosis of the gut microbiome and human IBD and associated colorectal cancer has not been well established. In the current study, we sought to characterize colon mucosa adherent microbiota using metaproteomics to understand the colon micro-environment and the host-microbiome interactions. Three groups of colon biopsies were included in our analysis: healthy controls, Non-progressors (IBD patients without dysplasia or cancer) and Progressors (IBD patients who have dysplasia or cancer). The biopsy samples were analyzed by LC MS/MS and the bacterial proteins were identified using the Human Microbiome Project (HMP) human gut microbiome database. The inferences of bacterial taxonomy, bacterial enzymes and Gene ontology (GO) pathways were processed through Unipept. Examining bacterial composition between different sample groups showed no statistically significant difference at the levels of phyla and classes. However, a significant reduction of Holdemanella biformis was observed when comparing Progressors vs Non-progressors. Holdemanella biformis has recently been proposed to be endogenous anti-tumourigenic bacterial strains. Decrease of this bacterial species in Progressors suggested that it may be a protective bacteria preventing the progression of IBD associated colorectal cancer. Analysis of Gene Ontology (GO) biological processes identified GO terms that were significantly different among the Progressor, Non-progressor and healthy groups. For example, the GO term ‘detoxification of arsenic containing substances’ was significantly underrepresented in the Progressor group compared to healthy and Non-progressor groups. Furthermore, several bacterial enzymes were significantly different between the three groups. In particular, oxidoreductases were significantly decreased in the Progressor group compared to healthy and Non-progressor groups. While the implications of these significantly enriched or depleted bacterial biological processes and bacterial enzymes in the neoplastic progression of IBD warrant further investigation, the results from our current study provide new insight into understanding how gut microbiota as a modulator of microenvironment may contribute to progression of IBD-associated colorectal cancer. Citation Format: Nobel Bhasin, Prerna Dabral, Victoria Poplaski, Lisa Lai, Hong-Yuan Tsai, Mary Bronner, Teresa Brentnall, John Valentine, Jordon March, Antone Opekun, Robert Britton, Pan Sheng, Ru Chen. Metaproteomic analysis of IBD associated colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5078.