Targeted Virome Deep Sequencing Reveals Frequent Herpesvirus Detection in Intestinal Biopsies of Intestinal Bowel Disease Patients

Background: The intestinal virome, a vital component of the gut microbiota, is increasingly recognized for its role in intestinal health and disease. Inflammatory bowel disease (IBD), including Crohn's disease, ulcerative colitis, and unclassified IBD (IBD-U), has been associated with microbial dysbiosis, yet the viral contribution remains underexplored. Methods: We conducted a retrospective metagenomic study on 56 residual intestinal biopsy samples from IBD patients using high-throughput sequencing with prior viral nucleic acid enrichment via probe-based capture. Bioinformatic analysis was performed using the Chan Zuckerberg ID platform. A total of 33 samples met stringent quality thresholds and were included in statistical analyses using Fisher's exact test. Results: Viruses were detected in 58.9% (33/56) of the biopsies, primarily members of the Herpesviridae family, including Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesviruses 6 and 7 (HHV-6, HHV-7). Coinfections were also identified. EBV was the most prevalent virus (60.6%), followed by HHV-7 (33.3%), CMV (21.2%), and HHV-6 (21.2%). Other viruses such as Norovirus and human papillomavirus (HPV) were detected at lower frequencies. No statistically significant associations were found between viral presence and IBD subtype (IBD vs. IBD-U). Conclusions: The frequent detection of herpesviruses, known to be absent in healthy intestinal viromes, suggests a potential role in disease progression or severity. Our findings highlight the value of metagenomic sequencing in characterizing the intestinal virome and underscore the need for further research, ideally including healthy controls, to assess the diagnostic or prognostic value of viral biomarkers in IBD. Keywords: intestinal virome, inflammatory bowel disease, metagenomics, viral enrichment, Herpesviridae, high-throughput sequencing.