Review Article

The Gut Microbiome in Inflammatory Bowel Disease—Avenues for Microbial Management

J. McIlroy; G. Ianiro; I. Mukhopadhya; R. Hansen; G. L. Hold


Aliment Pharmacol Ther. 2018;47(1):26-42. 

In This Article

The Role of the Virome

Newer methodological techniques in the metagenomic assessment of the gut virome as a composite entity has opened new avenues in our understanding of its role in the aetiopathogenesis of inflammatory bowel disease. Expansion of annotated viral databases and improved bioinformatic analysis have also increased the ability to correctly identify a larger cohort of these viruses. An initial study utilising epifluorescence microscopy was the first to suggest that there was an increase of bacteriophages in patients with CD as opposed to controls.[43] The predominant gut viruses identified were double-stranded DNA viruses in the Caudovirales order (including Podoviridae, Siphoviridae and Myoviridae). This finding was subsequently confirmed by a study utilising metagenomic assessment techniques on biopsy samples and gut washes in paediatric CD patients, wherein Wagner et al demonstrated that the maximum number of "viral hits" were seen in patients with CD.[44] Subsequently, a study by Wang et al looked at these changes in colonic biopsy samples from patients with CD and controls and showed alteration of virome abundance and diversity in the former group.[45]

The study by Pérez-Brocal was the first to document parallel changes between the bacterial and viral components of the gut microbiota in patients with inflammatory bowel disease. They demonstrated that there was a decrease in diversity and abundance of both the bacteria and viruses in patients with CD.[46] The most comprehensive analysis of the disease-specific alteration of the virome in IBD was reported by Norman et al.[47] The study demonstrated an expansion of Caudovirales bacteriophages in patients with both ulcerative colitis and CD but more importantly documented an inverse correlation with the bacterial component in both these diseases. However, the inverse relationship between the bacteria and the virome could not be reliably replicated in the validation USA cohorts in the study.[47] Subtle distinctions were noted between patients with CD and ulcerative colitis, wherein in the former group of subjects, the presence of Caudovirales were positively correlated with Enterobacteriaceae, Pasteurelloacaeae and Prevotellaceae but there was no such relationship noted with UC. Pérez-Brocal also demonstrated the positive representation of Synechococcus phage S CBS1 and Retroviridae family of viruses in patients with CD, with this propensity suggesting that they could be potential biomarkers.[46] Both these observations suggest that phenotypic differences in manifestations of ulcerative colitis and CD might be explained by the different changes in the gut virome. However, all these findings need to be consistently validated in other studies, and the bridge from association to causation still needs to be crossed.