Colorectal cancer is the second leading cause of cancer-related death in the United States and is a primary cause of morbidity and mortality throughout the world. Although the cause of colorectal cancer remains unclear, it has been strongly linked to gut bacterial communities. Viruses are another important component of the gut microbial community that have yet to be studied in colorectal cancer, despite their oncogenic potential. We evaluated the gut virome role in colorectal cancer using a cohort of 90 human subjects with either healthy, pre-cancerous, or cancerous colons. We utilized 16S rRNA gene, whole shotgun metagenomic, and purified virus metagenomic methods to compare the role of the virome to that of the bacterial community. We found that alpha and beta diversity metrics were insufficient for detecting an association between the virome and colorectal cancer, but virome-based classification models were both highly associated with colorectal cancer and outperformed those based on the bacterial community signature. Bacteriophages, not eukaryotic viruses, made up the majority of the CRC-associated virome, suggesting the community was indirectly linked to colorectal cancer, modulating bacterial community structure and functionality. Although the whole community was associated with colorectal cancer, virome members with broader host ranges had a more significant role in cancer development. These results suggest that phage communities are strongly associated with colorectal cancer, and that broadly tropic phages play a significant role. Because of its importance, the virome should be considered in future colorectal cancer studies, as well as other cancer types.
Sponsored by the Host Microbiome Initiative