title: 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.
  
  
  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.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Amandine
authors.initials: A
authors.lastname: Everard
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lazarevic
authors.forename: Muriel
authors.initials: M
authors.lastname: Derrien
authors.forename: Myriam
authors.initials: M
authors.lastname: Girard
authors.forename: Giulio G
authors.initials: GG
authors.lastname: Muccioli
authors.forename: Giulio M
authors.initials: GM
authors.lastname: Muccioli
authors.forename: Audrey M
authors.initials: AM
authors.lastname: Neyrinck
authors.forename: Sam
authors.initials: S
authors.lastname: Possemiers
authors.forename: Ann
authors.initials: A
authors.lastname: Van Holle
authors.forename: Patrice
authors.initials: P
authors.lastname: François
authors.forename: Willem M
authors.initials: WM
authors.lastname: de Vos
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Delzenne
authors.forename: Jacques
authors.initials: J
authors.lastname: Schrenzel
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
mesh_terms: D000818:Animals; D002432:Cecum / Q000382:microbiology*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D004041:Dietary Fats / Q000009:adverse effects; D019858:Enteroendocrine Cells / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D018149:Glucose Intolerance / Q000517:prevention & control; D006090:Gram-Negative Bacteria / Q000145:classification / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000145:classification / Q000302:isolation & purification; D006943:Hyperglycemia / Q000517:prevention & control*; D006949:Hyperlipidemias / Q000517:prevention & control*; D020738:Leptin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D058889:Molecular Typing; D009765:Obesity / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D056692:Prebiotics; D052336:Proglucagon / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D020738:Leptin; D056692:Prebiotics; D012333:RNA, Messenger; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1