Mechanistic roles and therapeutic potential of bacteriophages in inflammatory gastrointestinal diseases

Abstract

The gut virome, particularly its viral and phage components, is increasingly recognized as a key modulator of intestinal microbial dynamics in gastrointestinal inflammatory diseases. Beyond well-characterized bacterial dysbiosis, growing evidence suggests that virome alterations contribute to the development and progression of inflammatory bowel disease, metabolic dysfunction-associated steatohepatitis, alcoholic hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, and pancreatitis. As the most abundant viruses in the gut, bacteriophages influence microbial ecosystem stability and host immune responses through lytic and lysogenic interactions with bacterial populations. Amid the growing burden of multidrug-resistant infections and heightened interest in microbiota-based interventions, phage therapy has re-emerged as a viable strategy in both preclinical and translational contexts. This review synthesizes recent insights into bacteriophage dynamics in the context of major gastrointestinal and hepatopancreatic inflammatory diseases, highlighting potential compositional shifts, proposed mechanisms of phage-microbe interactions, and supportive evidence from animal models and early clinical applications. We also discussed the critical challenges that had to be addressed to enable clinical translation, including host range restrictions, resistance and safety concerns, immunogenicity, and delivery limitations, while emphasizing emerging strategies such as phage engineering, encapsulation technologies, and standardized regulatory frameworks.

Keywords

Gut virome / bacteriophages / phage therapy / digestive disease