Virulence genes are a signature of the microbiome in the colorectal tumor microenvironment

Abstract

BackgroundThe human gut microbiome is associated with the development of colon cancer, and recent studies have found changes in the composition of the microbial communities in cancer patients compared to healthy controls. However, host-bacteria interactions are mainly expected to occur in the cancer microenvironment, whereas current studies primarily use stool samples to survey the microbiome. Here, we highlight the major shifts in the colorectal tumor microbiome relative to that of matched normal colon tissue from the same individual, allowing us to survey the microbial communities at the tumor microenvironment, and provides intrinsic control for environmental and host genetic effects on the microbiome.\n\nResultsWe characterized the microbiome in 44 primary tumor and 44 patient-matched normal colon tissues. We find that tumors harbor distinct microbial communities compared to nearby healthy tissue. Our results show increased microbial diversity at the tumor microenvironment, with changes in the abundances of commensal and pathogenic bacterial taxa, including Fusobacterium and Providencia. While Fusobacteria has previously been implicated in CRC, Providencia is a novel tumor-associated agent, and has several features that make it a potential cancer driver, including a strong immunogenic LPS and an ability to damage colorectal tissue. Additionally, we identified a significant enrichment of virulence-associated genes in the colorectal cancer microenvironment.\n\nConclusionsThis work identifies bacterial taxa significantly correlated with colorectal cancer, including a novel finding of an elevated abundance of Providencia in the tumor microenvironment. We also describe several metabolic pathways and enzymes differentially present in the tumor associated microbiome, and show that the bacterial genes in the tumor microenvironment are enriched for virulence associated genes from the aggregate microbial community. This virulence enrichment indicates that the microbiome likely plays an active role in colorectal cancer development and/or progression. These reuslts provide a starting point for future prognostic and therapeutic research with the potential to improve patient outcomes.