LAUSR

Pathogenesis of Crohn's disease (CD) relates to gut microbiome dysbiosis. However, less is known about the viral microbiome, consisting of bacteriophages and eukaryotic viruses, in CD. Here, we profiled the stool virome, viral functions, and viral‐bacterial correlations that involved in CD pathogenesis. Metagenomics and metaviromics with novel viral identification and data analysis workflow were performed on stool of non‐CD household controls, CD flare and remission patients. Both bacteriome and DNA/RNA virome alterations were characterized and correlated with disease status. There was a decreased diversity and extreme heterogeneity in both DNA and RNA virome in CD. We observed CD‐specific dysbiosis in virome, particularly the prominent DNA eukaryotic Torque teno virus (TTV), disease‐associated Faecalibacterium phage and Escherichia phage, and RNA tomato diet‐related virus in CD, while some diverse prokaryotic viruses were more abundant in healthy subjects. Compared with the remission, inflammation‐associated eukaryotic TTV and prokaryotic Staphylococcus phages were predominated in the flare, and displayed a link with complications and multiple therapeutic approaches. Multiple viral functions, particularly functions of viral DNA replication, integration and modification as well as the eukaryotic TTV‐related capsid protein, were markedly enriched in CD. Furthermore, the virus–bacteria interactions became more specialized in CD, and the combination of bacteriome and virome composition provided better classification between CD and health. Our study presents a global view of the comprehensive viral component change in the CD patients' gut microbiome, and highlights the great potential of virome biomarkers in pathogenesis and accurate diagnostics of CD risk and disease status.