Abstract
Human viruses (those that infect human cells) have been associated with many cancers, largely due to their mutagenic and functionally manipulative abilities. Despite this, cancer microbiome studies have focused almost exclusively on bacteria instead of viruses. We began evaluating the cancer virome by focusing on colorectal cancer, a primary cause of morbidity and mortality throughout the world and a cancer linked to altered colonic bacterial community compositions but with an unknown association with the gut virome. We used 16S rRNA gene, whole shotgun metagenomic, and purified virus metagenomic sequencing of stool to evaluate the differences in human colorectal cancer virus and bacterial community composition. Through random forest modeling, we identified differences in the healthy and colorectal cancer viromes. The cancer-associated virome consisted primarily of temperate bacteriophages that were also predicted to be bacterium-virus community network hubs. These results provide foundational evidence that bacteriophage communities are associated with colorectal cancer and potentially impact cancer progression by altering the bacterial host communities.IMPORTANCE Colorectal cancer is a leading cause of cancer-related death in the United States and worldwide. Its risk and severity have been linked to colonic bacterial community composition. Although human-specific viruses have been linked to other cancers and diseases, little is known about colorectal cancer virus communities. We addressed this knowledge gap by identifying differences in colonic virus communities in the stool of colorectal cancer patients and how they compared to bacterial community differences. The results suggested an indirect role for the virome in impacting colorectal cancer by modulating the associated bacterial community. These findings both support the idea of a biological role for viruses in colorectal cancer and provide a new understanding of basic colorectal cancer etiology.
Highlights
Human viruses have been associated with many cancers, largely due to their mutagenic and functionally manipulative abilities
Work in this area has led to a proposed disease model in which bacteria colonize the colon, develop biofilms, promote inflammation, and enter an oncogenic synergy with the cancerous human cells [22]
Because previous work has identified shifts in which bacteria were most important at different stages of colorectal cancer [8, 20, 22], we explored whether shifts in the relative influences of phages could be detected between healthy, adenomatous, and cancerous colons
Summary
Human viruses (those that infect human cells) have been associated with many cancers, largely due to their mutagenic and functionally manipulative abilities. The strong association of bacterial communities with colorectal cancer (CRC), the previous identification of human-specific viruses that cause cancer, and the precedent for the virome to impact other human diseases suggest that colorectal cancer may be associated with altered virus communities. Growing evidence suggests that an important component of colorectal cancer etiology may be perturbations in the colonic bacterial community [8, 10, 11, 20, 21] Work in this area has led to a proposed disease model in which bacteria colonize the colon, develop biofilms, promote inflammation, and enter an oncogenic synergy with the cancerous human cells [22]. We evaluated disruptions in virus and bacterial community composition in a human cohort whose stool was sampled at the three relevant stages of cancer development: healthy, adenomatous, and cancerous
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