The gut virome in inflammatory bowel disease pathogenesis: From metagenomics to novel therapeutic approaches

Abstract

The association of intestinal dysbiosis with the pathogenesis of inflammatory bowel disease has been well established. Besides bacteria, microbiota comprises yeasts, archaea, protists and viruses, neglected actors in inflammatory bowel disease-associated microbiota. In the past, a great limitation in studying microbiota composition was the low sensitivity of sequencing technologies and that few computational approaches were sufficient to thoroughly analyse the whole microbiome. However, new cutting-edge technologies in nucleic acid sequencing, -omics analysis and the innovative statistics and bioinformatics pipelines made possible more sensitive and accurate metagenomics, ultimately identifying novel players in intestinal inflammation, including prokaryotic and eukaryotic viruses, that together form the gut virome. The discovery of peculiar inflammatory bowel disease-associated microbial strains will not only shed new light on inflammatory bowel disease aetiogenesis, they may also support the development of novel therapeutic strategies not merely treating symptoms, but precisely counteracting the primary cause of chronic intestinal inflammation.

Keywords: Inflammatory bowel disease; metagenomics; microbiota; next-generation sequencing; virome.

Figure 1.

Microbiota in inflammatory bowel disease (IBD). Healthy gut lumen is populated by different microbial species, including viruses, bacteria, yeasts, protists and archea (left panel). In IBD (right panel), epithelial barrier disruption leads to the translocation of microbes that colonize mucosa. This leads to the activation of both innate and adaptive immune responses, ultimately failing to be resolved and leading to chronic inflammation. This cartoon has been made exploiting Biorender and SMART websites (www.biorender.com, www.smart.servier.com)

Figure 2.

The multi-omic approach. Exploiting the computational biology, it will be possible to combine all -omic results and provide a composite picture of inflammatory bowel disease (IBD) etiopathogenesis.