Cangiano Lautaro R, Ipharraguerre Ignacio R, Guan Le Luo, Buss Lauralise N, Amorin-Hegedus Rocio, Chirivi Miguel, Contreras G Andres, Steele Michael A
Department of Animal Biosciences, University of Guelph, Guelph, ON, Canada.
Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany.
Front Microbiol. 2023 Aug 31;14:1210142. doi: 10.3389/fmicb.2023.1210142. eCollection 2023.
The objective of this study was to evaluate the effects of prophylactic neomycin administration on Holstein bull calves' intestinal microbiota, bile acid (BA) metabolism, and transcript abundance of genes related to BA metabolism. A total of 36 calves were blocked by body weight and assigned to either non-medicated milk replacer (CTL), or neomycin for 14 days (ST) or 28 days (LT) in their milk replacer. At the end of the study, calves were euthanized to collect tissue and digesta samples from the gastrointestinal tract, liver, and adipose tissue for analysis of intestinal microbial diversity, bile acid concentration and profile in various body tissues, and gene expression related to bile acid, lipid, carbohydrate metabolism, and inflammation. Calves that received prophylactic administration of neomycin for 28 d (LT) had reduced species richness (chao1 index), and tended to have reduced phylogenetic diversity in the ileum tissue. The relative abundance of , and in ileum and colon digesta were decreased in LT compared with CTL. Concentrations of primary, secondary, and total BA were increased by ST in ileal tissue. In plasma, ST and LT treatments had lower concentrations of secondary BA. Gene expression of the BA receptor was increased in ileum and liver by LT compared to CTL. The expression of and in the liver was increased in the ST group compared with CTL, and in adipose tissue, 5 genes related to triglyceride, gluconeogenesis, and immune activation were differentially expressed between CTL and ST. In conclusion, we provide evidence that prophylactic administration of neomycin leads to aberrant changes in BA concentration and profile in different compartments of the enterohepatic system through a process that possibly entails antimicrobial disruption of key bacterial groups, which persists even after cessation of neomycin administration. Additionally, we uncovered an apparent link between dysregulated BA metabolism and changes in lipid metabolism and immune activation in adipose tissue and liver.
本研究的目的是评估预防性给予新霉素对荷斯坦公牛犊肠道微生物群、胆汁酸（BA）代谢以及与BA代谢相关基因的转录丰度的影响。总共36头犊牛按体重进行分组，并分别给予不含药物的代乳品（CTL）、在代乳品中添加新霉素14天（ST）或28天（LT）。在研究结束时，对犊牛实施安乐死，以收集来自胃肠道、肝脏和脂肪组织的组织及消化物样本，用于分析肠道微生物多样性、不同身体组织中的胆汁酸浓度和谱型，以及与胆汁酸、脂质、碳水化合物代谢和炎症相关的基因表达。接受新霉素预防性给药28天（LT）的犊牛回肠组织中的物种丰富度（chao1指数）降低，且系统发育多样性有降低趋势。与CTL相比，LT组回肠和结肠消化物中的 、 和 的相对丰度降低。ST组回肠组织中初级、次级和总BA的浓度升高。在血浆中，ST和LT处理组的次级BA浓度较低。与CTL相比，LT组回肠和肝脏中BA受体 的基因表达增加。与CTL相比，ST组肝脏中 和 的表达增加，且在脂肪组织中，CTL和ST组之间有5个与甘油三酯、糖异生和免疫激活相关的基因差异表达。总之，我们提供的证据表明，预防性给予新霉素会通过可能涉及对抗关键细菌群的抗菌破坏的过程，导致肝肠系统不同隔室中BA浓度和谱型的异常变化，即使在停止给予新霉素后这种变化仍持续存在。此外，我们还发现BA代谢失调与脂肪组织和肝脏中脂质代谢及免疫激活变化之间存在明显联系。
