Bacteriophages as Phagobiotics: Scientific Rationale and Translational Boundaries for Gut Microbiome Modulation.

Most translational work on bacteriophages has focused on antibacterial therapy or food biocontrol. A third use case is scientifically plausible but remains insufficiently defined: the intentional use of characterized phages to modulate gut microbial communities without infection-treatment claims. In this review, the term "phagobiotics" is used for defined, purified and process-controlled bacteriophages or phage cocktails intended for selective gut microbiota modulation. The concept is evaluated across natural human phage exposure, the gut phageome, mechanisms of phage-mediated community modulation, human intervention studies, preclinical models, manufacturing quality and regulatory boundaries. Current evidence supports biological plausibility and indicates that oral phage exposure can be well tolerated and, in some contexts, can selectively affect target bacterial groups without broad microbiota disruption. Generalized clinical efficacy and broad microbiome-support claims, however, remain insufficiently established. Microbiological-modulation claims require target-linked evidence, whereas claims to treat, prevent or cure disease or replace antibiotics fall outside the proposed non-therapeutic category. A proportionate framework is proposed in which natural exposure and food-use precedents inform, but do not determine, the safety rationale; product-specific controls focus on identity, purity, production-host control, manufacturing consistency, stability, genomic characterization and claim-linked evidence. Regulatory classification remains case-specific and depends on intended use, product format, target population and claims.