Abstract
The role of gut microbiota, especially viruses, in colorectal cancer (CRC) pathogenesis remains unclear. This study investigated the interplay between gut microbiota and CRC development. We developed a viral/bacterial sequence analysis pipeline to reanalyze gut metagenomic datasets from eight CRC studies. A multisample co-occurrence network was constructed to delineate microbiota species interconnections. Our analysis confirmed dysbiosis in CRC patients and revealed enrichment of viral species, particularly those hosted by Lactococcus and Escherichia. These viruses were identified as central hubs in the multikingdom interaction network. We developed a network-based model using single sample networks (SSN) that distinguished CRC patients from controls with an area under the curve (AUC) of 0.93. Models combining relative abundance and SSN assessment achieved an AUC of 0.97, outperforming SSN-based models without viral data. This study highlights the crucial role of viruses in the gut microbiome network and their potential as targets for CRC prevention and intervention. Our approach offers a new perspective on noninvasive diagnostic criteria for CRC.