Mechanisms and Application of Bacteriophages in Regulating Intestinal Health of Livestock and Poultry.

The escalating crisis of antibiotic resistance has driven the global livestock and poultry industry to seek effective alternatives. Bacteriophages (phages) are promising candidates because their high host specificity allows targeted elimination of key intestinal pathogens, including Salmonella, Campylobacter, pathogenic Escherichia coli, and Clostridium perfringens, while sparing commensal microbiota. This review summarizes the mechanisms by which phages promote intestinal health in livestock and poultry, covering pathogen lysis, modulation of gut microbiota, reinforcement of the intestinal mucosal barrier, and regulation of host immune responses. Evidence from broiler chickens, weaned piglets, and ruminants shows that phage therapy can improve growth performance and help control diseases such as necrotic enteritis and edema disease. We further discuss how administration route, dosage, timing, and formulation affect intestinal delivery, and how encapsulation systems such as microcapsules and liposomes improve phage survival under gastrointestinal conditions. Strategies to delay resistance evolution through phage cocktails, and combinations of phages with probiotics or plant extracts, are also evaluated, with a staged screening framework proposed for assessing compatibility prior to field deployment. Because positive results dominate the controlled-trial literature, we critically appraise failed, limited, and non-durable in vivo trials, attributing these outcomes to rapid clearance, anti-phage immunity, inappropriate dosing, and spatial exclusion coupled with ecological mismatch. Commercial translation additionally depends on scalable production and downstream removal of endotoxins and host cell proteins at acceptable cost. Overcoming these challenges would allow phage-based interventions to serve as precision antibiotic alternatives that support sustainable animal farming and global food security.