Microbiome-phage interactions in inflammatory bowel disease

Background: Inflammatory bowel disease (IBD) constitutes a group of auto-inflammatory disorders that impact the gastrointestinal tract and other systemic organs. The gut microbiome contributes to IBD pathology through multiple mechanisms. Bacteriophages (hereafter termed phages) are viruses that are able to specifically infect bacteria. Considered as part of the gut microbiome, phages may impact the bacterial community structure in various clinical contexts. Additionally, exogenous phage administration may represent a means of suppressing IBD-associated pathobionts; however, the utilization of phage therapy remains at an early developmental phase.

Objectives: Herein, we summarize the latest advances in understanding endogenous phage impacts on the gut microbiome in a healthy gut and in IBD. We highlight the prospect of phage utilization as a targeted mode of pathobiont eradication, for preventing and treating IBD manifestations and complications.

Sources: Selected peer-reviewed publications regarding the role of phages in a healthy gut and in IBD, published between 2013 and 2022.

Content: The human gut microbiome is increasingly suggested to play a significant role in the onset and progression of multiple non-communicable diseases such as IBD. Several studies suggest that this effect may be mediated by discrete disease-contributing commensals. However, the eradication of such pathogenic bacteria remains a daunting unmet task. Altered community structure in IBD may be influenced by blooms of phages within the gut bacterial ecosystem. Moreover, combinations of phages specifically targeting disease-contributing pathobiont strain clades may be harnessed as potential eradication treatment preventing and treating IBD, while bearing minimal adverse impacts on the surrounding bacterial microbiome.

Implications: Understanding the endogenous phage-gut commensal interactions in a healthy gut and in IBD may enable phage utilization in precision gut microbiome editing, towards treating IBD and other non-communicable microbiome-associated diseases. Nevertheless, developing phage combination-mediated IBD pathobiont eradication treatment modalities will likely necessitate better strain-level bacterial target identification and resolution of treatment-related challenges, such as phage delivery, off-target effects, and bacterial resistance.