Work

Repeated-Dose 28-Day Oral Toxicity Study of a Salmonella enterica Serovar Typhimurium Bacteriophage Cocktail (SE.PC) in BALB/c Mice

Year: 2026

Type: article

Abstract: 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.

Source: PHAGE

DOI: 10.1177/26416549261448405

Authors: Yee Fan Tan, Prasanna Mutusamy, Sivachandran Parimannan, Heera Rajandas, Parasuraman Subramani

Institutions: AIMST University, University of Copenhagen

Language: English

Topic: Bacteriophages and microbial interactions

Subfield: Ecology

Field: Environmental Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: Kementerian Pendidikan Malaysia