Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice.

Abstract

OBJECTIVE:

To investigate deep and comprehensive analysis of gut microbial communities and biological parameters after prebiotic administration in obese and diabetic mice.

RESEARCH DESIGN AND METHODS:

Genetic (ob/ob) or diet-induced obese and diabetic mice were chronically fed with prebiotic-enriched diet or with a control diet. Extensive gut microbiota analyses, including quantitative PCR, pyrosequencing of the 16S rRNA, and phylogenetic microarrays, were performed in ob/ob mice. The impact of gut microbiota modulation on leptin sensitivity was investigated in diet-induced leptin-resistant mice. Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models.

RESULTS:

In ob/ob mice, prebiotic feeding decreased Firmicutes and increased Bacteroidetes phyla, but also changed 102 distinct taxa, 16 of which displayed a >10-fold change in abundance. In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation. In high fat-fed mice, prebiotic treatment improved leptin sensitivity as well as metabolic parameters.

CONCLUSIONS:

We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice. By profiling the gut microbiota, we identified a catalog of putative bacterial targets that may affect host metabolism in obesity and diabetes.

• Authors: Amandine Everard, Vladimir Lazarevic, Muriel Derrien, Myriam Girard, Giulio G Muccioli, Giulio M Muccioli, Audrey M Neyrinck, Sam Possemiers, Ann Van Holle, Patrice François, Willem M de Vos, Nathalie M Delzenne, Jacques Schrenzel, Patrice D Cani
• Journal: Diabetes (Diabetes) Vol. 60 Issue 11 Pg. 2775-86 (Nov 2011) ISSN: 1939-327X [Electronic] United States
• PMID: 21933985 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Fats
• Leptin
• Prebiotics
• RNA, Messenger
• Proglucagon
• Glucagon-Like Peptide 1

Topics

• Animals
• Cecum (microbiology)
• Colon (metabolism, pathology)
• Diabetes Mellitus, Type 2 (blood, diet therapy, metabolism, pathology)
• Dietary Fats (adverse effects)
• Enteroendocrine Cells (metabolism, pathology)
• Gene Expression Regulation
• Glucagon-Like Peptide 1 (blood)
• Glucose Intolerance (prevention & control)
• Gram-Negative Bacteria (classification, isolation & purification)
• Gram-Positive Bacteria (classification, isolation & purification)
• Hyperglycemia (prevention & control)
• Hyperlipidemias (prevention & control)
• Leptin (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Molecular Typing
• Obesity (blood, diet therapy, metabolism, pathology)
• Prebiotics
• Proglucagon (genetics, metabolism)
• RNA, Messenger (metabolism)