Abstract

Antimicrobial resistance has intensified the global search for alternatives to conventional antibiotics. Bacteriophages offer one of the few mechanistically distinct options, yet the literature remains fragmented across separate clinical, veterinary, food, agricultural, environmental, and aquaculture fields. Most reviews focus on a single application area and rarely compare multiple fields under a unified analytical framework. The cumulative evidence is therefore stronger than any single literature suggests, and recurring barriers remain invisible from within any single field. This integrative review examines bacteriophage applications across seven fields through a One Health perspective. It evaluates seven recurring translational barriers within a comparative cross-domain framework and assesses how each barrier manifests across the different application areas. Three findings stand out. First, regulatory fragmentation, not technical failure, is the dominant barrier in every field examined, with at least four distinct regulatory paradigms operating in parallel. Second, formulation and environmental persistence, rather than phage isolation, now drive most active commercial development; the scalability of personalised cocktails remains incompatible with conventional drug-approval pathways. Third, many of the operational tools needed to address these barriers are already in routine use within at least one field, so the practical task is cross-domain transfer rather than new development. Bacteriophage applications can no longer be treated as an isolated niche within any single field. The evidence positions them as an integrated, mechanistically distinct One Health intervention that complements the classical antibiotic, vaccine, and biosecurity-based control of bacterial infection.