Background: Phage therapy is a promising alternative for drug-resistant Salmonella , but safety data for repeated doses are limited. This study investigated the sub-chronic safety of SE.PC, a candidate Salmonella enterica serovar Typhimurium phage cocktail, in a non-specific pathogen-free (non-SPF) model, which contains a naturally occurring microbiota, to evaluate systemic safety under physiologically relevant conditions. We tested a range of phage doses to determine if there are any differences in tolerance. Materials and Methods: During a 28-day repeated-dose oral toxicity study, SE.PC was administered via weekly gavage to male and female non-SPF BALB/c mice across three different phage doses (2.43 × 10 9 , 4.85 × 10 9 , and 9.70 × 10 9 plaque-forming units/mL). Clinical signs, body weight, hematology, biochemistry, and histopathology were assessed. Results: Across all three administered phage dose groups, no mortality was recorded, and all mice exhibited normal clinical signs and growth. Hematological and biochemical values remained within baseline ranges. Histopathology revealed no treatment-related lesions; isolated findings were deemed incidental or adaptive. Conclusion: Evidence supports that SE.PC is well tolerated. This study demonstrates a strong safety profile, supporting the advancement of SE.PC as a biocontrol agent.
Tan et al. (2026) studied this question.