Viral and Bacterial Communities of Colorectal Cancer

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. Its risk has been linked to changes in colonic bacterial community composition. Viruses are another important component of the colonic microbial community, however they have yet to be studied in colorectal cancer despite their oncogenic potential. We evaluated the colorectal cancer virome (virus community) in stool using a cohort of 90 human subjects with either healthy, adenomatous (precancerous), or cancerous colons. We utilized 16S rRNA gene, whole shotgun metagenomic, and purified virus metagenomic sequencing methods to compare the colorectal cancer virome to the bacterial community. We identified no detectable difference in diversity (alpha or beta) between healthy, adenomatous, or cancerous colonic samples, but more sophisticated random forest models identified striking changes in the virus community. The majority of the cancer-associated virome consisted of temperate bacteriophages, suggesting that the community was indirectly linked to colorectal cancer by modulating bacterial community structure and function. Our data suggested that the influential phages did not exclusively infect influential bacteria, but rather acted through the community as a whole. These results provide foundational evidence that bacteriophage communities are associated with colorectal cancer and likely impact cancer progression by altering the bacterial host communities.