Metagenomic analysis of intestinal mucosa revealed a specific eukaryotic gut virome signature in early-diagnosed inflammatory bowel disease

Intestinal dysbiosis is one of the causes underlying the pathogenesis of inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD). Besides bacteria, microbiota comprises both prokaryotic and eukaryotic viruses, that together compose the gut virome. Few works have defined the viral composition of stools, while the virome populating intestinal mucosae from early-diagnosed IBD patients has never been studied. Here we show that, by in-depth metagenomic analysis of RNA-Seq data obtained from gut mucosae of young treatment-naive patients, early-diagnosed for CD and UC, and from healthy subjects (Ctrl), UC patients display significantly higher levels of eukaryotic Hepadnaviridae transcripts by comparison with both Ctrl and CD patients, whereas CD patients show increased abundance of Hepeviridae versus Ctrl. Moreover, we found that UC gut mucosa is characterized by lower levels of Polydnaviridae and Tymoviridae, whereas the mucosa of patients with CD showed a reduced abundance of Virgaviridae. Our findings support the idea that certain eukaryotic viruses might trigger intestinal inflammation and contribute to IBD pathogenesis and pave the way not only for the discovery of novel diagnostic biomarkers but also for the development of anti-viral drugs for the treatment of IBD.