Bacteriophages in humans: From discovery and mechanisms to therapeutic promise in combating disease

ABSTRACT: Since the discovery of bacteriophages over a century ago, bacteriophages have evolved from fundamental biological models into promising therapeutic agents, especially in the era of antimicrobial resistance and in the treatment of human diseases. This article systematically reviews the key milestones in phage research and application at both international and Chinese fronts. It examines the evolving understanding of phage-bacterium interactions, which provides the development of targeted phage-based biocontrol and therapeutic strategies. Particular emphasis is placed on recent advances linking phages to human diseases, including their potential roles in gut microbiota modulation and chronic disease contexts. Despite promise, substantial challenges remain. The article concludes by discussing critical future directions, emphasizing the need for identifying key microbial targets in diseases, integrating phage therapy with emerging technologies to accelerate clinical translation, and exploring dietary phage interventions for disease prevention.