Rodrigues Richard R, Greer Renee L, Dong Xiaoxi, DSouza Karen N, Gurung Manoj, Wu Jia Y, Morgun Andrey, Shulzhenko Natalia
Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, United States.
Department of Biomedical Sciences, Oregon State University, Corvallis, OR, United States.
Front Microbiol. 2017 Nov 22;8:2306. doi: 10.3389/fmicb.2017.02306. eCollection 2017.
The gut microbiome plays an important role in health and disease. Antibiotics are known to alter gut microbiota, yet their effects on glucose tolerance in lean, normoglycemic mice have not been widely investigated. In this study, we aimed to explore mechanisms by which treatment of lean mice with antibiotics (ampicillin, metronidazole, neomycin, vancomycin, or their cocktail) influences the microbiome and glucose metabolism. Specifically, we sought to: (i) study the effects on body weight, fasting glucose, glucose tolerance, and fasting insulin, (ii) examine the changes in expression of key genes of the bile acid and glucose metabolic pathways in the liver and ileum, (iii) identify the shifts in the cecal microbiota, and (iv) infer interactions between gene expression, microbiome, and the metabolic parameters. Treatment with individual or a cocktail of antibiotics reduced fasting glucose but did not affect body weight. Glucose tolerance changed upon treatment with cocktail, ampicillin, or vancomycin as indicated by reduced area under the curve of the glucose tolerance test. Antibiotic treatment changed gene expression in the ileum and liver, and shifted the alpha and beta diversities of gut microbiota. Network analyses revealed associations between with fasting glucose and liver farsenoid X receptor (Fxr) in the top ranked host-microbial interactions, suggesting possible mechanisms by which this bacterium can mediate systemic changes in glucose metabolism. We observed to be positively and negatively correlated with hepatic Fxr and Glucose 6-phosphatase, respectively. Overall, our transkingdom network approach is a useful hypothesis generating strategy that offers insights into mechanisms by which antibiotics can regulate glucose tolerance in non-obese healthy animals. Experimental validation of our predicted microbe-phenotype interactions can help identify mechanisms by which antibiotics affect host phenotypes and gut microbiota.
肠道微生物群在健康和疾病中起着重要作用。已知抗生素会改变肠道微生物群，但它们对瘦型、血糖正常小鼠的葡萄糖耐量的影响尚未得到广泛研究。在本研究中，我们旨在探索用抗生素（氨苄青霉素、甲硝唑、新霉素、万古霉素或其组合）治疗瘦型小鼠影响微生物群和葡萄糖代谢的机制。具体而言，我们试图：（i）研究对体重、空腹血糖、葡萄糖耐量和空腹胰岛素的影响，（ii）检查肝脏和回肠中胆汁酸和葡萄糖代谢途径关键基因表达的变化，（iii）确定盲肠微生物群的变化，以及（iv）推断基因表达、微生物群和代谢参数之间的相互作用。单独使用或联合使用抗生素治疗可降低空腹血糖，但不影响体重。如葡萄糖耐量试验曲线下面积减少所示，联合使用、氨苄青霉素或万古霉素治疗后葡萄糖耐量发生了变化。抗生素治疗改变了回肠和肝脏中的基因表达，并改变了肠道微生物群的α和β多样性。网络分析显示，在排名靠前的宿主 - 微生物相互作用中，[此处原文可能有缺失内容]与空腹血糖和肝脏类法尼醇X受体（Fxr）之间存在关联，提示该细菌介导葡萄糖代谢全身变化的可能机制。我们观察到[此处原文可能有缺失内容]分别与肝脏Fxr和葡萄糖6磷酸酶呈正相关和负相关。总体而言，我们的跨领域网络方法是一种有用的产生假设的策略，可深入了解抗生素调节非肥胖健康动物葡萄糖耐量的机制。对我们预测的微生物 - 表型相互作用进行实验验证有助于确定抗生素影响宿主表型和肠道微生物群的机制。
