The successful use of virulent (lytic) bacteriophages (phages) in preventing and treating neonatal enterotoxigenic Escherichia coli infections in calves, lambs and pigs has prompted investigation of other applications of phage therapy in food animals. While results have been very variable, some indicate that phage therapy is potentially useful in virulent Salmonella and E. coli infections in chickens, calves and pigs, and in control of the food-borne pathogens Salmonella and Campylobacter jejuni in chickens and E. coli O157:H7 in cattle. However, more rigorous and comprehensive research is required to determine the true potential of phage therapy. Particular challenges include the selection and characterization of phages, practical modes of administration, and development of formulations that maintain the viability of phages for administration. Also, meaningful evaluation of phage therapy will require animal studies that closely represent the intended use, and will include thorough investigation of the emergence and characteristics of phage resistant bacteria. As well, effective use will require understanding the ecology and dynamics of the endemic and therapeutic phages and their interactions with target bacteria in the farm environment. In the event that the potential of phage therapy is realized, adoption will depend on its efficacy and complementarity relative to other interventions. Another potential challenge will be regulatory approval.

Cattle are a major reservoir of Escherichia coli O157:H7, an important zoonotic pathogen that causes hemorrhagic colitis and hemolytic uremic syndrome (HUS). Colonization of cattle occurs predominantly in the large intestine, and may especially target follicle-associated epithelium (FAE) in the terminal rectum. Bacterial colonization involves induction of attaching–effacing (A/E) lesions, mediated by type III secreted proteins and an outer membrane protein called intimin. ToxB, encoded on plasmid pO157, contributes to adherence of E. coli O157:H7 through promotion of the production and/or secretion of type III secreted proteins. Production of type III secreted proteins and intestinal colonization appear to involve quorum-sensing mechanisms. In the human host, E. coli O157:H7 may have a preference for FAE in the distal small intestine. The H7 flagellum induces production of chemokines such as interleukin 8, and neutrophilic infiltration of the intestinal mucosa, which in turn may enhance Shiga toxin (Stx) uptake across the intestinal epithelium. Both Stx and cytokine responses play critical roles in the induction of the vascular lesions that underlie hemorrhagic colitis and HUS. In cattle, Stx binds to intestinal crypt cells and submucosal lymphocytes but not vascular endothelium. The role played by Stx in cattle may be to suppress mucosal immunity, yet enhance other effects that promote intestinal colonization.