In a significant development, phage therapy is emerging as a solution against antimicrobial-resistant bacteria, marking a shift from conventional antibiotic treatments. Recognizing the intricate connection between bacterial microbiota and gastrointestinal/liver diseases, researchers are aiming to leverage phages’ precise bactericidal action for targeted editing of the gut microbiota.

Fujiki et al. provided an overview of the fundamental virological characteristics of phages and recent discoveries regarding the composition of the intestinal phageome and its alterations linked to liver diseases. Additionally, they examined preclinical and clinical investigations evaluating the efficacy of phage therapy in managing gastrointestinal and liver disorders, while also discussing future outlooks and obstacles in this field.

Preclinical studies indicate that targeted removal of harmful bacteria by phages can lead to improvements in various conditions like inflammatory bowel disease and liver diseases induced by ethanol consumption. However, well-designed clinical trials are necessary to enhance our understanding of phage therapy’s potential in treating gastrointestinal and liver diseases.

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Advantages of phages over antibiotics in the context of addressing bacterial infections and dysbiosis.

(A) Antibiotics have been conventionally applied to bacterial infections; however, the use of antibiotics has led to the emergence of antimicrobial-resistant strains of bacteria, and there are cases in which antibiotics are not expected to be effective. On the other hand, killing of antimicrobial-resistant bacteria by phages is expected to be more effective because phages possess completely distinct bactericidal mechanisms compared to antibiotics. However, the narrow host range of phages may limit their application in the treatment of infectious diseases.

(B) There is concern that the use of conventional antibiotics may kill even useful microbes in the human body inducing dysbiosis. On the other hand, phages have a very specific host range. Therefore, phages have the potential to selectively eliminate pathobionts in the dysbiotic bacterial microbiota of patients. AMR, antimicrobial resistance.

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