Colorectal cancer (CRC) is a leading cause of cancer-related deaths in both the USA and the world. Recent research has demonstrated the involvement of the gut microbiota in CRC development and progression. Microbial biomarkers of disease have focused primarily on the bacterial component of the microbiome; however, the viral portion of the microbiome, consisting of both bacteriophages and eukaryotic viruses, together known as the virome, has been lesser studied. Here we review the recent advancements in high-throughput sequencing (HTS) technologies and bioinformatics, which have enabled scientists to better understand how viruses might influence the development of colorectal cancer. We discuss the contemporary findings revealing modulations in the virome and their correlation with CRC development and progression. While a variety of challenges still face viral HTS detection in clinical specimens, we consider herein numerous next steps for future basic and clinical research. Clinicians need to move away from a single infectious agent model for disease etiology by grasping new, more encompassing etiological paradigms, in which communities of various microbial components interact with each other and the host. The reporting and indexing of patient health information, socioeconomic data, and other relevant metadata will enable identification of predictive variables and covariates of viral presence and CRC development. Altogether, the virome has a more profound role in carcinogenesis and cancer progression than once thought, and viruses, specific for either human cells or bacteria, are clinically relevant in understanding CRC pathology, patient prognosis, and treatment development.
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