Potential probiotic application of a novel commensal E. coli strain with antagonistic activity against different enteric pathogens.

Diarrheal diseases remain a leading cause of global morbidity and mortality, with treatment options increasingly compromised by the global rise of multidrug-resistant (MDR) pathogens. Furthermore, the absence of effective vaccines against many causative agents leaves large populations vulnerable. This critical gap necessitates the development of novel alternatives that can function both prophylactically to prevent infection and therapeutically to treat established disease. Here we investigated the probiotic potential of a commensal Escherichia coli strain HK220822 (HK5) which was isolated from a healthy human, as a potential live biotherapeutic. Comprehensive genomic and phenotypic characterization established a robust safety profile, confirming the absence of key virulence genes while demonstrating essential probiotic traits, including high tolerance to gastrointestinal stressors like acid and bile. The functional efficacy of E. coli (HK5) was validated in murine infection models. Prophylactic administration prior to pathogen exposure significantly inhibited intestinal colonization by Salmonella Typhimurium, Shigella flexneri 2a, and Vibrio cholerae (El Tor O1 strain). Moreover, HK5 demonstrated therapeutic potential, significantly reducing pathogen shedding when administered to previously infected animals. These findings establish this commensal E. coli (HK5) as a potent probiotic candidate with dual preventative and therapeutic efficacy, offering a promising non-antibiotic strategy to combat diarrheal diseases.