show Abstracthide AbstractThis study investigates the effects of antibiotic-induced gut microbiome perturbations on the conjugative transfer of antibiotic resistance genes (ARGs) in a murine model. Three different antibiotic regimens were administered to simulate clinical, veterinary, and heavy-dose treatments, with a control group receiving no antibiotics. Our aim was to elucidate the relationship between the level of gut dysbiosis and the mobility of ARGs, particularly focusing on the dissemination mechanisms of multi-drug resistance IncA/C plasmids. Mice were inoculated with Salmonella enterica serovar Typhimurium (recipient) followed by a S. Heidelberg chicken farm isolate (donor) carrying the resistance plasmid. The study monitored colonization densities, plasmid transfer events, and changes in the gut microbiota composition and ARG abundance through fecal sampling, quantitative PCR, and 16S rRNA amplicon and whole-genome sequencing. This research underscores the importance of considering gut microbiome health in antibiotic stewardship and AMR mitigation strategies.