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This Article Full Text Full Text (PDF) All Versions of this Article: fj.07-102723v1 22/7/2416    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Membrez, M. Articles by Chou, C. J. PubMed PubMed Citation Articles by Membrez, M. Articles by Chou, C. J.

Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice

Mathieu Membrez^*, Florence Blancher^*, Muriel Jaquet^*, Rodrigo Bibiloni^*, Patrice D. Cani, Rémy G. Burcelin, Irène Corthesy^*, Katherine Macé^* and Chieh Jason Chou^*,1

^* Nestlé Research Center, Lausanne, Switzerland;

Université Catholique de Louvain, Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Brussels, Belgium; and

Institute of Molecular Medicine Rangueil (12 MR), INSERM U858, IFR31, Toulouse, France

¹Correspondence: Nestlé Research Center, P.O. Box 44, CH 1000 Lausanne, Switzerland. E-mail: chieh-jason.chou{at}rdls.nestle.com

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.—Membrez, M., Blancher, F., Jaquet, M., Bibiloni, R., Cani, P. D., Burcelin, R. G., Corthesy, I., Macé, K., Chou, C. J. Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice.

Key Words: lipopolysaccharide • hepatic steatosis • liver glycogen • TNF-