title: A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice.
abstract: OBJECTIVE
  The increasing prevalence of obesity and type 2 diabetes (T2D) demonstrates the failure of conventional treatments to curb these diseases. The gut microbiota has been put forward as a key player in the pathophysiology of diet-induced T2D. Importantly, cranberry (Vaccinium macrocarpon Aiton) is associated with a number of beneficial health effects. We aimed to investigate the metabolic impact of a cranberry extract (CE) on high fat/high sucrose (HFHS)-fed mice and to determine whether its consequent antidiabetic effects are related to modulations in the gut microbiota.
  
  
  METHODS
  C57BL/6J mice were fed either a chow or a HFHS diet. HFHS-fed mice were gavaged daily either with vehicle (water) or CE (200 mg/kg) for 8 weeks. The composition of the gut microbiota was assessed by analysing 16S rRNA gene sequences with 454 pyrosequencing.
  
  
  RESULTS
  CE treatment was found to reduce HFHS-induced weight gain and visceral obesity. CE treatment also decreased liver weight and triglyceride accumulation in association with blunted hepatic oxidative stress and inflammation. CE administration improved insulin sensitivity, as revealed by improved insulin tolerance, lower homeostasis model assessment of insulin resistance and decreased glucose-induced hyperinsulinaemia during an oral glucose tolerance test. CE treatment was found to lower intestinal triglyceride content and to alleviate intestinal inflammation and oxidative stress. Interestingly, CE treatment markedly increased the proportion of the mucin-degrading bacterium Akkermansia in our metagenomic samples.
  
  
  CONCLUSIONS
  CE exerts beneficial metabolic effects through improving HFHS diet-induced features of the metabolic syndrome, which is associated with a proportional increase in Akkermansia spp.
authors: Department of Medicine, Faculty of Medicine, Cardiology Axis of the Quebec Heart and Lung Institute, Quebec, Quebec, Canada Institute of Nutrition and Functional Foods, Laval University, Quebec, Quebec, Canada.
authors: Fernando F
authors: FF
authors: Anhê
authors: Institute of Nutrition and Functional Foods, Laval University, Quebec, Quebec, Canada.
authors: Denis
authors: D
authors: Roy
authors: Department of Medicine, Faculty of Medicine, Cardiology Axis of the Quebec Heart and Lung Institute, Quebec, Quebec, Canada Institute of Nutrition and Functional Foods, Laval University, Quebec, Quebec, Canada.
authors: Geneviève
authors: G
authors: Pilon
authors: Institute of Nutrition and Functional Foods, Laval University, Quebec, Quebec, Canada.
authors: Stéphanie
authors: S
authors: Dudonné
authors: Institute of Nutrition and Functional Foods, Laval University, Quebec, Quebec, Canada.
authors: Sébastien
authors: S
authors: Matamoros
authors: Institute of Nutrition and Functional Foods, Laval University, Quebec, Quebec, Canada.
authors: Thibault V
authors: TV
authors: Varin
authors: Research Centre, Sainte-Justine Hospital, Montreal, Quebec, Canada.
authors: Carole
authors: C
authors: Garofalo
authors: Research Centre, Sainte-Justine Hospital, Montreal, Quebec, Canada.
authors: Quentin
authors: Q
authors: Moine
authors: Institute of Nutrition and Functional Foods, Laval University, Quebec, Quebec, Canada.
authors: Yves
authors: Y
authors: Desjardins
authors: Research Centre, Sainte-Justine Hospital, Montreal, Quebec, Canada Department of Nutrition, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
authors: Emile
authors: E
authors: Levy
authors: Department of Medicine, Faculty of Medicine, Cardiology Axis of the Quebec Heart and Lung Institute, Quebec, Quebec, Canada Institute of Nutrition and Functional Foods, Laval University, Quebec, Quebec, Canada.
authors: André
authors: A
authors: Marette
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D019446:Endotoxemia / Q000209:etiology / Q000517:prevention & control; D004751:Enteritis / Q000188:drug therapy* / Q000382:microbiology*; D006505:Hepatitis / Q000517:prevention & control; D006706:Homeostasis / Q000187:drug effects; D007333:Insulin Resistance; D007422:Intestines / Q000382:microbiology; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects; D056128:Obesity, Abdominal / Q000209:etiology / Q000517:prevention & control*; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols / Q000032:analysis / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism; D029799:Vaccinium macrocarpon / Q000737:chemistry*; D061327:Verrucomicrobia / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D008055:Lipids; D008070:Lipopolysaccharides; D010936:Plant Extracts; D059808:Polyphenols; D014280:Triglycerides
keywords: Diabetes Mellitus; Intestinal Bacteria; Intestinal Permeability; Obesity; Prebiotic