Antibiotic perturbation causes delayed resilience in the intestinal virome

NOD2 plays a key role in shaping the gut microbiome, and loss-of-function variants in the NOD2 gene are associated with an increased risk of developing Crohn’s disease. To improve our understanding of the role of the enteric intestinal virome in IBD, we longitudinally characterized the resilience of the viral community in fecal samples from wild-type (WT) C57BL/6J and knock-out (KO) NOD2 mice in response to an antibiotic perturbation. Sequencing of viral-like-particles (VLPs) demonstrated both a high diversity and high inter-individual variation in the murine gut virome composed of eukaryotic viruses and bacteriophages. Antibiotics also had a significant impact on the gut murine virome causing a delayed resilience independent of genotype. However, compositional shifts in the virome and bacteriome were highly correlated, indicating a possible role of the virome in IBD. Bacteriophage species may be playing an important role in either upregulating or downregulating the bacterial community, and restoring a healthy virome may therefore be a central goal of microbiota-targeted therapies. Importantly, the phage community rarely harbored antibiotic resistance genes (ARGs).