The intestinal virome in IBD

▸ Norman JM, Handley SA, Baldridge MT, et al. Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 2015;160:1–14.

Defining disease-specific changes in the gut microbiota has been the topic of great debate for many years in the context of IBD. Almost exclusively, studies have focused on defining changes in gut bacterial populations. Recently, the remit has broadened to assess the fungal component, the mycome, and also the viral component, the virome. The enteric virome consists mainly of bacteriophage belonging to Caudovirales and Microviridae, as well as some eukaryotic viruses. These interact with the host to potentially exacerbate IBD. In the case of the more abundant bacteriophage component, they are thought to play a direct role in intestinal physiology or to change the bacterial microbiome through predator-prey relationships. This study characterised the normal human and IBD enteric virome and demonstrated that its richness actually increased in Crohn's disease (CD) and UC despite a decrease in bacterial richness and diversity. These findings were demonstrated in three geographically distinct patient populations. The primary change in the IBD virome was a significant expansion of Caudovirales bacteriophage, which was speculated to be owing to either induction of prophage from commensal microbes or introduction of environmentally acquired new viruses. Either option could increase horizontal gene transfer within gut bacteria including genes responsible for pathogenesis or antibiotic resistance. It is also possible that expansion of the virome could lead to lysis of their bacterial hosts which could trigger proinflammatory signalling cascades. This is the first demonstration showing that changes in the enteric virome occur in CD and UC, raising the possibility that these changes may contribute to disease pathogenesis. The study provides clear evidence that we need greater appreciation of transkingdom interactions within the microbiome. The study also highlights the need to …