title: Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction.
abstract: To investigate the beneficial role of prebiotics on endothelial dysfunction, an early key marker of cardiovascular diseases, in an original mouse model linking steatosis and endothelial dysfunction.
  
  
  
  We examined the contribution of the gut microbiota to vascular dysfunction observed in apolipoprotein E knockout (Apoe-/-) mice fed an n-3 polyunsaturated fatty acid (PUFA)-depleted diet for 12 weeks with or without inulin-type fructans (ITFs) supplementation for the last 15 days. Mesenteric and carotid arteries were isolated to evaluate endothelium-dependent relaxation ex vivo. Caecal microbiota composition (Illumina Sequencing of the 16S rRNA gene) and key pathways/mediators involved in the control of vascular function, including bile acid (BA) profiling, gut and liver key gene expression, nitric oxide and gut hormones production were also assessed.
  
  
  
  ITF supplementation totally reverses endothelial dysfunction in mesenteric and carotid arteries of n-3 PUFA-depleted Apoe-/-mice via activation of the nitric oxide (NO) synthase/NO pathway. Gut microbiota changes induced by prebiotic treatment consist in increased NO-producing bacteria, replenishment of abundance inAkkermansiaand decreased abundance in bacterial taxa involved in secondary BA synthesis. Changes in gut and liver gene expression also occur upon ITFs suggesting increased glucagon-like peptide 1 production and BA turnover as drivers of endothelium function preservation.
  
  
  
  We demonstrate for the first time that ITF improve endothelial dysfunction, implicating a short-term adaptation of both gut microbiota and key gut peptides. If confirmed in humans, prebiotics could be proposed as a novel approach in the prevention of metabolic disorders-related cardiovascular diseases.
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Emilie
authors.initials: E
authors.lastname: Catry
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Laure B
authors.initials: LB
authors.lastname: Bindels
authors.affiliation: European Genomic Institute for Diabetes (EGID), Univ Lille, Lille, France.|INSERM UMR 1011, Lille, France.|Institut Pasteur de Lille, Lille, France.|CHU de Lille, Lille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Tailleux
authors.affiliation: European Genomic Institute for Diabetes (EGID), Univ Lille, Lille, France.|INSERM UMR 1011, Lille, France.|Institut Pasteur de Lille, Lille, France.|CHU de Lille, Lille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lestavel
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Audrey M
authors.initials: AM
authors.lastname: Neyrinck
authors.affiliation: Centre Universitaire de Mesures et d'Analyses, Univ. Lille, Lille, France.|EA 7365 GRITA, Lille, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Goossens
authors.affiliation: Pole of Pharmacology and Therapeutics, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Irina
authors.initials: I
authors.lastname: Lobysheva
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.|Walloon Excellence in Life sciences and BIOtechnology (WELBIO), Belgium.
authors.forename: Hubert
authors.initials: H
authors.lastname: Plovier
authors.affiliation: Pole of Experimental Medicine, de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Essaghir
authors.affiliation: Pole of Experimental Medicine, de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Demoulin
authors.affiliation: IREC Imaging Platform, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bouzin
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Pachikian
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.|Walloon Excellence in Life sciences and BIOtechnology (WELBIO), Belgium.
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
authors.affiliation: European Genomic Institute for Diabetes (EGID), Univ Lille, Lille, France.|INSERM UMR 1011, Lille, France.|Institut Pasteur de Lille, Lille, France.|CHU de Lille, Lille, France.
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.affiliation: Pole of Pharmacology and Therapeutics, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Dessy
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Delzenne
mesh_terms: D000626:Aminopeptidases / Q000235:genetics; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics; D001419:Bacteria / Q000187:drug effects; D001647:Bile Acids and Salts / Q000096:biosynthesis / Q000097:blood; D002339:Carotid Arteries / Q000502:physiology; D002432:Cecum / Q000382:microbiology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000172:deficiency; D005630:Fructans / Q000494:pharmacology*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000096:biosynthesis; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D000074085:Mice, Knockout, ApoE; D009496:Neurotensin / Q000235:genetics; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics; D056692:Prebiotics; D052336:Proglucagon / Q000235:genetics; D027981:Symporters / Q000235:genetics; D014664:Vasodilation
chemical_list: D023181:Antimicrobial Cationic Peptides; D001647:Bile Acids and Salts; D015525:Fatty Acids, Omega-3; D005630:Fructans; D029363:Organic Anion Transporters, Sodium-Dependent; D056692:Prebiotics; D027981:Symporters; C071908:sodium-bile acid cotransporter; D009569:Nitric Oxide; D009496:Neurotensin; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1; D019001:Nitric Oxide Synthase; D000626:Aminopeptidases
keywords: BILE ACID METABOLISM; CARDIOVASCULAR DISEASE; ENDOCRINE HORMONES; INTESTINAL MICROBIOLOGY; PREBIOTIC