Characterizing the gut virome in ulcerative colitis and crohn's disease: signatures of disease severity.

Virome richness and diversity were reduced in severe UC and CD compared with healthy controls, while mild cases showed values closer to healthy individuals.

• Cross-sectional observational study conducted in Tabriz, Iran with fifty participants divided into five groups: mild UC, severe UC, mild CD, severe CD, and healthy controls (n=10 per group).
• Stool samples were processed for viral nucleic acid extraction and analyzed using metagenomic next-generation sequencing.
• Bioinformatics pipelines included diversity assessment, taxonomic profiling, functional annotation, and discriminant analysis (LEfSe).
• The gradient of diversity loss tracked with disease severity, with mild IBD cases showing intermediate values between healthy controls and severe IBD.

Taxonomic profiling revealed depletion of crAss-like phages and Microviridae in IBD patients.

• crAss-like phages, considered core members of the healthy gut virome, were depleted across IBD groups.
• Microviridae were also reduced in IBD compared to healthy controls.
• These phages are generally considered to be associated with microbial balance and protective functions in the healthy gut.
• LEfSe discriminant analysis was used to identify taxonomic signatures differentiating IBD groups from controls.

Caudovirales families, specifically Siphoviridae and Myoviridae, were enriched in IBD patients.

• Siphoviridae and Myoviridae were enriched in IBD groups relative to healthy controls.
• These families belong to the order Caudovirales and are double-stranded DNA bacteriophages.
• Enrichment of these families was identified through metagenomic taxonomic profiling and LEfSe analysis.
• Their enrichment in IBD may be associated with altered bacterial host communities and amplified host inflammation.

Among eukaryotic viruses, Anelloviridae were prominent in severe IBD and Herpesviridae were enriched specifically in severe UC.

• Anelloviridae abundance was elevated in both severe UC and severe CD groups.
• Herpesviridae enrichment was found specifically in severe UC but not specifically highlighted in severe CD.
• These eukaryotic viral signatures were identified through metagenomic next-generation sequencing and taxonomic profiling.
• The selective enrichment of eukaryotic viruses in severe disease groups suggests a potential role in disease severity stratification.

Functional annotation revealed enrichment of structural and lytic phage proteins in severe IBD groups, while lysogeny-associated domains were more abundant in healthy controls.

• Structural and lytic phage functional proteins were enriched in severe UC and severe CD groups.
• Lysogeny-associated functional domains were more abundant in healthy control samples.
• This functional shift suggests a transition from temperate (lysogenic) to lytic phage activity associated with IBD severity.
• Functional annotation was performed as part of the bioinformatics pipeline applied to metagenomic sequencing data.

Random forest classifiers based on viral features achieved an AUC of 0.89 for distinguishing IBD from controls and 0.83 for classifying mild versus severe disease.

• Predictive modeling was performed using random forest classifiers.
• The model achieved an AUC of 0.89 for distinguishing IBD patients from healthy controls.
• The model achieved an AUC of 0.83 for classifying mild versus severe disease.
• The authors described these results as 'appropriate accuracy' for virome-based classification.
• These results suggest virome features may have potential as biomarkers for non-invasive diagnosis and severity stratification in IBD.

The study authors concluded that virome features may have potential as biomarkers for non-invasive diagnosis and severity stratification in IBD, but require validation in larger and longitudinal cohorts.

• The study was cross-sectional with a total of fifty participants across five groups (n=10 per group), limiting generalizability.
• The authors explicitly noted the need for 'validation in larger and longitudinal cohorts.'
• The study was conducted at a single center in Tabriz, Iran.
• The findings collectively suggest that the gut virome is altered in IBD in a severity-dependent manner.