Combined pre- and probiotic interventions used in fecal samples of various animal origins to decolonize MDR bacteria. PreProBiotics

Multidrug-resistant (MDR) pathogens, especially Escherichia coli and Klebsiella pneumoniae, are increasingly prevalent in human, veterinary, wildlife, and environmental contexts. While microbiota-based interventions show promise in mitigating the spread of MDR bacteria within and between hosts, their application beyond preclinical mouse models remains limited. Here, we assessed in situ colonization resistance (CR) against MDR pathogens in feces from livestock and wildlife animals. In addition, we evaluated the efficacy of a probiotic candidate and selected prebiotics against MDR bacteria. Results revealed varying CR levels across wildlife, livestock, and human samples. The probiotic candidate exhibited inhibitory effects against MDR E. coli and K. pneumoniae across different host origins, while the effect of prebiotics remained limited. We delineated signatures associated with enhanced natural CR and probiotic efficacy using culture-dependent and- independent methods. Within the One Health framework, this study underscores the potential of prophylactic probiotic use in curbing MDR pathogen spread, particularly in livestock.