Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice.
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.
Membrez
Mathieu
M
Nestlé Research Center, P.O. Box 44, CH 1000 Lausanne, Switzerland.
Blancher
Florence
F
Jaquet
Muriel
M
Bibiloni
Rodrigo
R
Cani
Patrice D
PD
Burcelin
Rémy G
RG
Corthesy
Irène
I
Macé
Katherine
K
Chou
Chieh Jason
CJ
D000667:Ampicillin / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001439:Bacteroides / Q000187:drug effects* / Q000502:physiology; D001644:Bifidobacterium / Q000187:drug effects* / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000503:physiopathology; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000502:physiology; D007778:Lactobacillus / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008820:Mice, Obese; D008826:Microbial Sensitivity Tests; D009643:Norfloxacin / Q000494:pharmacology*; D009765:Obesity / Q000382:microbiology / Q000503:physiopathology
D000900:Anti-Bacterial Agents; D000667:Ampicillin; D009643:Norfloxacin