Find in Library

The purpose of this study was to establish the clinical breakpoint (CBP) of apramycin (APR) against <i>Salmonella</i> in swine and evaluate its effect on intestinal microbiota. The CBP was established based on three cutoff values of wild-type cutoff value (CO_WT), pharmacokinetic-pharmadynamic (PK/PD) cutoff value (CO_PD) and clinical cutoff value (CO_CL). The effect of the optimized dose regimen based on ex vivo PK/PD study. The evolution of the ileum flora was determined by the <i>16rRNA</i> gene sequencing and bioinformatics. This study firstly established the CO_WT, CO_PD in ileum, and CO_CL of APR against swine <i>Salmonella</i>, the value of these cutoffs were 32 µg/mL, 32 µg/mL and 8 µg/mL, respectively. According to the guiding principle of the Clinical Laboratory Standards Institute (CLSI), the final CBP in ileum was 32 µg/mL. Our results revealed the main evolution route in the composition of ileum microbiota of diarrheic piglets treated by APR. The change of the abundances of <i>Bacteroidetes</i> and <i>Euryarchaeota</i> was the most obvious during the evolution process. <i>Methanobrevibacter</i>, <i>Prevotella</i>, <i>S24-7</i> and <i>Ruminococcaceae</i> were obtained as the highest abundance genus. The abundance of <i>Methanobrevibacter</i> increased significantly when APR treatment carried and decreased in cure and withdrawal period groups. The abundance of <i>Prevotella</i> in the tested groups was significantly lower than that in the healthy group. A decreased of abundance in <i>S24-7</i> was observed after <i>Salmonella</i> infection and increased slightly after cure. <i>Ruminococcaceae</i> increased significantly after <i>Salmonella</i> infection and decreased significantly after APR treatment. In addition, the genera of <i>Methanobrevibacter</i> and <i>Prevotella</i> were defined as the key node. Valine, leucine and isoleucine biosynthesis, D-Glutamine and D-glutamate metabolism, D-Alanine metabolism, Peptidoglycan and amino acids biosynthesis were the top five Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the ileum microbiota of piglets during the <i>Salmonella</i> infection and APR treatment process. Our study extended the understanding of dynamic shift of gut microbes during diarrheic piglets treated by APR.