Bacteriocins have been steadily reported as potential agents that may contribute, in different ways, to overcome antimicrobial drug resistance. Here, holoxenic NMRI-F mice microbiota, their body weight recovery and histopathological alterations of organs like colon, spleen and liver were examined in mice intraperitoneally infected with 10 8 cfu of a clinical methicillin-resistant Staphylococcus aureus (MRSA-1), and treated with enterocin DD14 alone (165 mg/kg), erythromycin alone (100 mg/kg) or their combination. Animals that received both antimicrobials presented a better body weight recovery than other groups. Less pronounced histopathological alterations were observed in mice MRSA-infected and treated with bacteriocin than in those MRSA-infected but untreated or MRSA-infected and treated with erythromycin. Noteworthy, these alterations were absent when mice were treated with MRSA-infected and treated with both antibacterial agents. Furthermore, the genus richness was significantly lower in mice infected and treated with erythromycin, compared to mice infected and treated with both antimicrobials. The beta-diversity analysis showed that non-infected mice and those infected and treated with both antimicrobials, stand apart from the other groups as supported in a NMDS model. This in vivo study shows the relevance of bacteriocin, or bacteriocin-antibiotic formulation in protecting colonic, liver and spleen soft tissues and controlling the mouse gut microbiota, following MRSA infection.