背景:在先前的研究中,100%的狗服用恩诺沙星和甲硝唑,发生与抗生素相关的胃肠道体征。合生元部分缓解了体征。这个随机的目标,双盲,安慰剂对照试验是比较服用恩诺沙星和甲硝唑的狗的粪便微生物组和代谢组,然后是安慰剂或细菌/酵母合生元组合。方法:将22只健康研究犬随机分为两个治疗组。有三个研究期:基线,治疗,和冲洗。狗服用恩诺沙星(10mg/kgqd)和甲硝唑(12.5mg/kgBID),1小时后服用安慰剂或市售合生元组合(BID),每个操作系统21天,此后重新评估56天。在第5-7天(基线)收集粪便样品,26-28和82-84。通过qPCR和16SrRNA基因测序分析粪便微生物组;使用飞行时间质谱来确定代谢组学谱。分割图重复测量混合模型ANOVA用于比较治疗组之间的结果。P<0.05被认为是显著的,Benjamini和Hochberg的错误发现率用于调整多次比较。结果:随着时间的推移,两个治疗组的α多样性指标差异显著,在82-84天不完全恢复。β多样性和菌群失调指数随时间和治疗组之间存在显着差异,安慰剂组的狗在第82-84天恢复不完全。在15个属中发现了显着的按时间分组的相互作用,包括Adlercreutzia,双歧杆菌,Slackia,Turicibacter,梭状芽胞杆菌(包括希氏梭菌)[Ruminococus],丹毒科_g_,[Eubacterium],和丁二弧菌科_g_。六个属存在并发组和时间效应,包括Collinsella,Ruminocycaceae_g_,还有Prevotella.代谢物谱因时间而异,group,以及28、20和192种代谢物的时间,分别。这些包括短链脂肪酸,胆汁酸,色氨酸,鞘脂,苯甲酸,和肉桂酸代谢物,以及岩藻糖和乙醇胺。许多分类群和代谢物的变化持续到第82-84天。结论:服用抗生素会导致犬持续的菌群失调和代谢异常。注意到许多分类群和代谢物的显着按时间组相互作用,在服用合生元的狗中,可能降低抗生素诱导的胃肠道作用。
Background: Antibiotic-associated gastrointestinal signs occurred in 100% of dogs administered enrofloxacin with metronidazole in a previous
study, and signs partially were mitigated by synbiotics. The objective of this randomized, double-blinded, placebo-controlled
trial was to compare the fecal microbiome and metabolome of dogs administered enrofloxacin and metronidazole, followed by either a placebo or a bacterial/yeast synbiotic combination. Methods: Twenty-two healthy research dogs were randomized to two treatment groups. There were three
study periods: baseline, treatment, and washout. Dogs were administered enrofloxacin (10 mg/kg qd) and metronidazole (12.5 mg/kg BID), followed 1 h later by placebo or a commercially-available synbiotic combination (BID), per os for 21 days with reevaluation 56 days thereafter. Fecal samples were collected on days 5-7 (baseline), 26-28, and 82-84. The fecal microbiome was analyzed by qPCR and sequencing of 16S rRNA genes; time-of-flight mass spectrometry was used to determine metabolomic profiles. Split plot repeated measures mixed model ANOVA was used to compare results between treatment groups. P < 0.05 was considered significant, with Benjamini and Hochberg\'s False Discovery Rate used to adjust for multiple comparisons. Results: Alpha diversity metrics differed significantly over time in both treatment groups, with incomplete recovery by days 82-84. Beta diversity and the dysbiosis index differed significantly over time and between treatment groups, with incomplete recovery at days 82-84 for dogs in the placebo group. Significant group-by-time interactions were noted for 15 genera, including Adlercreutzia, Bifidobacterium, Slackia, Turicibacter, Clostridium (including C. hiranonis) [Ruminococcus], Erysipelotrichaceae_g_, [Eubacterium], and Succinivibrionaceae_g_. Concurrent group and time effects were present for six genera, including Collinsella, Ruminococcaceae_g_, and Prevotella. Metabolite profiles differed significantly by group-by-time, group, and time for 28, 20, and 192 metabolites, respectively. These included short-chain fatty acid, bile acid, tryptophan, sphingolipid, benzoic acid, and cinnaminic acid metabolites, as well as fucose and ethanolamine. Changes in many taxa and metabolites persisted through days 82-84. Conclusion: Antibiotic administration causes sustained dysbiosis and dysmetabolism in dogs. Significant group-by-time interactions were noted for a number of taxa and metabolites, potentially contributing to decreased antibiotic-induced gastrointestinal effects in dogs administered synbiotics.