Investigating the use of a 16-member defined microbial community to treat Salmonella Typhimurium infection in a mouse model
Abstract
Introduction: Non-typhoidal Salmonella is a leading cause of foodborne illness worldwide, accounting for more than 150 million infections annually and representing a significant global health burden. Current treatment strategies are primarily supportive, relying on oral rehydration therapy, while antibiotics are reserved for severe or high-risk cases. However, antibiotic therapy offers limited benefits for reducing illness duration, symptom severity, or pathogen carriage and may prolong bacterial shedding while contributing to the development of antibiotic resistance. These limitations have driven increasing need for alternative therapeutic approaches against Salmonella, including microbiota-modulating interventions such as probiotics. Methods: We evaluated the prophylactic potential of a 16-member defined microbial community (DMC-16) against Salmonella enterica serovar Typhimurium (S. Tm.) in vivo. C57BL/6 mice were pre-treated with streptomycin and administered either DMC-16 or vehicle control prior to oral challenge with S. Tm. or control. Disease progression was monitored over a 7-day post-infection period through daily weight measurements. At study endpoint, tissues were collected and analyzed to assess pathogen burden and indicators of infection severity. Results: Prophylactic administration of DMC-16 improved survival and significantly reduced colonic S. Tm. pathogen burden in infected mice. However, DMC-16 did not significantly affect weight loss, splenic S. Tm. burden, colonic shortening, or splenomegaly following infection. Conclusion: These findings demonstrate that DMC-16 limits intestinal colonization of S. Tm. and improves survival outcomes, supporting its potential as a prophylactic microbiota-based therapy against Salmonella infection. This work highlights the therapeutic potential of bacterial-based interventions in S. Tm. infection, and contributes to ongoing efforts to develop novel non-antibiotic strategies for the prevention and treatment of gastrointestinal diseases.Faculty Supervisor: Dr. Prameet Sheth