Membrez Mathieu, Blancher Florence, Jaquet Muriel, Bibiloni Rodrigo, Cani Patrice D, Burcelin Rémy G, Corthesy Irène, Macé Katherine, Chou Chieh Jason
Nestlé Research Center, P.O. Box 44, CH 1000 Lausanne, Switzerland.
FASEB J. 2008 Jul;22(7):2416-26. doi: 10.1096/fj.07-102723. Epub 2008 Mar 7.
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 1 g/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.
近期数据表明，肠道微生物群在脂肪积累中起重要作用。然而，尚不清楚肠道微生物群是否参与2型糖尿病的病理生理过程。为评估这一问题，我们在两种不同的胰岛素抵抗小鼠模型中通过给予抗生素来调节肠道微生物群。剂量确定研究结果显示，诺氟沙星和氨苄西林联合使用，剂量为1 g/L时，能最大程度地抑制ob/ob小鼠盲肠需氧菌和厌氧菌数量。在用抗生素联合治疗2周后，ob/ob小鼠以及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著改善。血糖控制的改善与食物摄入量或肥胖无关，因为配对喂养的ob/ob小鼠与对照ob/ob小鼠一样存在葡萄糖不耐受。肝脏甘油三酯减少和肝糖原增加与治疗小鼠葡萄糖耐量的改善相关。血浆脂多糖的减少和脂联素的增加进一步支持了抗生素治疗对ob/ob小鼠的抗糖尿病作用。总之，调节肠道微生物群通过改变参与炎症和代谢的肝脏和肠道基因的表达，以及改变宿主的激素、炎症和代谢状态，改善了小鼠的葡萄糖耐量。
