Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice
Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice
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DOI：
10.1096/fj.07-102723
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发表时间：
2008-07-01
期刊：
影响因子：
4.8
通讯作者：
Chou, Chieh Jason
中科院分区：
文献类型：
--
作者：
Membrez, Mathieu;Blancher, Florence;Chou, Chieh Jason
最近的数据表明，肠道微生物群在脂肪积累中起着重要作用。然而，肠道微生物群是否参与2型糖尿病的病理生理尚不清楚。为了评估这个问题，我们在两种不同的胰岛素抵抗小鼠模型中通过给药抗生素来调节肠道微生物群。剂量测定研究结果表明，诺氟沙星和氨苄西林在1g/L的剂量下，最大限度地抑制了ob/ob小鼠盲肠好氧和厌氧细菌的数量。在抗生素联合干预2周后，ob/ob和饮食诱导的肥胖和胰岛素抵抗小鼠的空腹血糖和口服葡萄糖耐量均有显着改善。血糖控制的改善与食物摄入或肥胖无关，因为配对喂养的ob/ob小鼠与对照组的ob/ob小鼠一样葡萄糖耐受不良。肝脏甘油三酯的降低和肝糖原的增加与治疗小鼠葡萄糖耐量的改善相关。同时血浆脂多糖的减少和脂联素的增加进一步支持抗生素治疗ob/ob小鼠的降糖作用。综上所述，肠道菌群的调节通过改变参与炎症和代谢的肝脏和肠道基因的表达，以及通过改变宿主的激素、炎症和代谢状态来改善小鼠的糖耐量。
Recent data suggest that the gut microbiota plays a significant role in fat accumulation. However, it is not clear whether gut microbiota is involved in the pathophysiology of type 2 diabetes. To assess this issue, we modulated gut microbiota via antibiotics administration in two different mouse models with insulin resistance. Results from dose-determination studies showed that a combination of norfloxacin and ampicillin, at a dose of 1g/L, maximally suppressed the numbers of cecal aerobic and anaerobic bacteria in ob/ob mice. After a 2-wk intervention with the antibiotic combination, both ob/ob and diet-induced obese and insulin-resistant mice showed a significant improvement in fasting glycemia and oral glucose tolerance. The improved glycemic control was independent of food intake or adiposity because pair-fed ob/ob mice were as glucose intolerant as the control ob/ob mice. Reduced liver triglycerides and increased liver glycogen correlated with improved glucose tolerance in the treated mice. Concomitant reduction of plasma lipopolysaccharides and increase of adiponectin further supported the antidiabetic effects of the antibiotic treatment in ob/ob mice. In summary, modulation of gut microbiota ameliorated glucose tolerance of mice by altering the expression of hepatic and intestinal genes involved in inflammation and metabolism, and by changing the hormonal, inflammatory, and metabolic status of the host.