National Reference Laboratory of Veterinary Drug Residues and MOA Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, China.
MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan 430070, China.
Int J Mol Sci. 2022 Jan 26;23(3):1424. doi: 10.3390/ijms23031424.
The purpose of this study was to establish the clinical breakpoint (CBP) of apramycin (APR) against in swine and evaluate its effect on intestinal microbiota. The CBP was established based on three cutoff values of wild-type cutoff value (CO), pharmacokinetic-pharmadynamic (PK/PD) cutoff value (CO) and clinical cutoff value (CO). The effect of the optimized dose regimen based on ex vivo PK/PD study. The evolution of the ileum flora was determined by the gene sequencing and bioinformatics. This study firstly established the CO, CO in ileum, and CO of APR against swine , 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 and was the most obvious during the evolution process. , , and were obtained as the highest abundance genus. The abundance of increased significantly when APR treatment carried and decreased in cure and withdrawal period groups. The abundance of in the tested groups was significantly lower than that in the healthy group. A decreased of abundance in was observed after infection and increased slightly after cure. increased significantly after infection and decreased significantly after APR treatment. In addition, the genera of and 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 infection and APR treatment process. Our study extended the understanding of dynamic shift of gut microbes during diarrheic piglets treated by APR.
本研究旨在建立大观霉素（APR）对猪的临床折点（CBP），并评估其对肠道微生物群的影响。CBP 是基于野生型截止值（CO）、药代动力学-药效学（PK/PD）截止值（CO）和临床截止值（CO）三个截止值建立的。根据体外 PK/PD 研究优化剂量方案的效果。通过 16S rRNA 基因测序和生物信息学分析来确定回肠菌群的演变。本研究首次建立了 APR 对猪 的 CO、CO 和 CO，这些截止值分别为 32µg/mL、32µg/mL 和 8µg/mL。根据临床实验室标准化研究所（CLSI）的指导原则，最终的回肠 CBP 为 32µg/mL。我们的研究结果揭示了 APR 治疗腹泻仔猪回肠菌群组成的主要演变途径。在进化过程中， 和 的丰度变化最为明显。 和 是获得的丰度最高的属。APR 治疗携带时 丰度显著增加，治愈和停药期组减少。与健康组相比，各试验组 的丰度显著降低。感染 后 丰度减少，治愈后略有增加。感染后 显著增加，APR 治疗后显著减少。此外， 属和 属被定义为关键节点。缬氨酸、亮氨酸和异亮氨酸生物合成、D-谷氨酰胺和 D-谷氨酸代谢、D-丙氨酸代谢、肽聚糖和氨基酸生物合成是仔猪感染 和 APR 治疗过程中回肠微生物群中前 5 个京都基因与基因组百科全书（KEGG）通路。本研究扩展了对 APR 治疗腹泻仔猪肠道微生物动态变化的认识。
