PMID- 28377388
OWN - NLM
STAT- MEDLINE
DCOM- 20180309
LR  - 20220129
IS  - 1468-3288 (Electronic)
IS  - 0017-5749 (Print)
IS  - 0017-5749 (Linking)
VI  - 67
IP  - 2
DP  - 2018 Feb
TI  - Targeting the gut microbiota with inulin-type fructans: preclinical demonstration 
      of a novel approach in the management of endothelial dysfunction.
PG  - 271-283
LID - 10.1136/gutjnl-2016-313316 [doi]
AB  - OBJECTIVE: 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. DESIGN: 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. RESULTS: 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 in Akkermansia and 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. 
      CONCLUSIONS: 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.
CI  - Published by the BMJ Publishing Group Limited. For permission to use (where not 
      already granted under a licence) please go to 
      http://www.bmj.com/company/products-services/rights-and-licensing/.
FAU - Catry, Emilie
AU  - Catry E
AD  - Metabolism and Nutrition Research Group, Louvain Drug Research Institute, 
      Universite catholique de Louvain, Brussels, Belgium.
FAU - Bindels, Laure B
AU  - Bindels LB
AD  - Metabolism and Nutrition Research Group, Louvain Drug Research Institute, 
      Universite catholique de Louvain, Brussels, Belgium.
FAU - Tailleux, Anne
AU  - Tailleux A
AD  - European Genomic Institute for Diabetes (EGID), Univ Lille, Lille, France.
AD  - INSERM UMR 1011, Lille, France.
AD  - Institut Pasteur de Lille, Lille, France.
AD  - CHU de Lille, Lille, France.
FAU - Lestavel, Sophie
AU  - Lestavel S
AD  - European Genomic Institute for Diabetes (EGID), Univ Lille, Lille, France.
AD  - INSERM UMR 1011, Lille, France.
AD  - Institut Pasteur de Lille, Lille, France.
AD  - CHU de Lille, Lille, France.
FAU - Neyrinck, Audrey M
AU  - Neyrinck AM
AD  - Metabolism and Nutrition Research Group, Louvain Drug Research Institute, 
      Universite catholique de Louvain, Brussels, Belgium.
FAU - Goossens, Jean-Francois
AU  - Goossens JF
AD  - Centre Universitaire de Mesures et d'Analyses, Univ. Lille, Lille, France.
AD  - EA 7365 GRITA, Lille, France.
FAU - Lobysheva, Irina
AU  - Lobysheva I
AD  - Pole of Pharmacology and Therapeutics, Institut de Recherche Experimentale et 
      Clinique, Universite catholique de Louvain, Brussels, Belgium.
FAU - Plovier, Hubert
AU  - Plovier H
AD  - Metabolism and Nutrition Research Group, Louvain Drug Research Institute, 
      Universite catholique de Louvain, Brussels, Belgium.
AD  - Walloon Excellence in Life sciences and BIOtechnology (WELBIO), Belgium.
FAU - Essaghir, Ahmed
AU  - Essaghir A
AD  - Pole of Experimental Medicine, de Duve Institute, Universite catholique de 
      Louvain, Brussels, Belgium.
FAU - Demoulin, Jean-Baptiste
AU  - Demoulin JB
AD  - Pole of Experimental Medicine, de Duve Institute, Universite catholique de 
      Louvain, Brussels, Belgium.
FAU - Bouzin, Caroline
AU  - Bouzin C
AD  - IREC Imaging Platform, Universite catholique de Louvain, Brussels, Belgium.
FAU - Pachikian, Barbara D
AU  - Pachikian BD
AD  - Metabolism and Nutrition Research Group, Louvain Drug Research Institute, 
      Universite catholique de Louvain, Brussels, Belgium.
FAU - Cani, Patrice D
AU  - Cani PD
AD  - Metabolism and Nutrition Research Group, Louvain Drug Research Institute, 
      Universite catholique de Louvain, Brussels, Belgium.
AD  - Walloon Excellence in Life sciences and BIOtechnology (WELBIO), Belgium.
FAU - Staels, Bart
AU  - Staels B
AD  - European Genomic Institute for Diabetes (EGID), Univ Lille, Lille, France.
AD  - INSERM UMR 1011, Lille, France.
AD  - Institut Pasteur de Lille, Lille, France.
AD  - CHU de Lille, Lille, France.
FAU - Dessy, Chantal
AU  - Dessy C
AD  - Pole of Pharmacology and Therapeutics, Institut de Recherche Experimentale et 
      Clinique, Universite catholique de Louvain, Brussels, Belgium.
FAU - Delzenne, Nathalie M
AU  - Delzenne NM
AD  - Metabolism and Nutrition Research Group, Louvain Drug Research Institute, 
      Universite catholique de Louvain, Brussels, Belgium.
LA  - eng
GR  - 336452/ERC_/European Research Council/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170404
PL  - England
TA  - Gut
JT  - Gut
JID - 2985108R
RN  - 0 (Antimicrobial Cationic Peptides)
RN  - 0 (Bile Acids and Salts)
RN  - 0 (Fatty Acids, Omega-3)
RN  - 0 (Fructans)
RN  - 0 (Organic Anion Transporters, Sodium-Dependent)
RN  - 0 (Prebiotics)
RN  - 0 (Symporters)
RN  - 145420-23-1 (sodium-bile acid cotransporter)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 39379-15-2 (Neurotensin)
RN  - 55963-74-1 (Proglucagon)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 3.4.11.- (Aminopeptidases)
SB  - IM
CIN - Nat Rev Gastroenterol Hepatol. 2017 Jul;14(7):392-394. PMID: 28559592
CIN - Gut. 2018 Feb;67(2):201-202. PMID: 28659350
CIN - Gut. 2019 Apr;68(4):764-765. PMID: 29618497
MH  - Aminopeptidases/genetics
MH  - Animals
MH  - Antimicrobial Cationic Peptides/genetics
MH  - Bacteria/drug effects
MH  - Bile Acids and Salts/biosynthesis/blood
MH  - Carotid Arteries/physiology
MH  - Cecum/microbiology
MH  - Dietary Supplements
MH  - Disease Models, Animal
MH  - Endothelium, Vascular/*drug effects/*physiopathology
MH  - Fatty Acids, Omega-3/administration & dosage/deficiency
MH  - Fructans/*pharmacology
MH  - Gastrointestinal Microbiome/*drug effects
MH  - Gene Expression/drug effects
MH  - Glucagon-Like Peptide 1/biosynthesis
MH  - Male
MH  - Mesenteric Arteries/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout, ApoE
MH  - Neurotensin/genetics
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase/metabolism
MH  - Organic Anion Transporters, Sodium-Dependent/genetics
MH  - *Prebiotics
MH  - Proglucagon/genetics
MH  - Symporters/genetics
MH  - Vasodilation
PMC - PMC5868295
OTO - NOTNLM
OT  - BILE ACID METABOLISM
OT  - CARDIOVASCULAR DISEASE
OT  - ENDOCRINE HORMONES
OT  - INTESTINAL MICROBIOLOGY
OT  - PREBIOTIC
COIS- Competing interests: None declared.
EDAT- 2017/04/06 06:00
MHDA- 2018/03/10 06:00
PMCR- 2018/03/26
CRDT- 2017/04/06 06:00
PHST- 2016/10/27 00:00 [received]
PHST- 2017/02/17 00:00 [revised]
PHST- 2017/02/20 00:00 [accepted]
PHST- 2017/04/06 06:00 [pubmed]
PHST- 2018/03/10 06:00 [medline]
PHST- 2017/04/06 06:00 [entrez]
PHST- 2018/03/26 00:00 [pmc-release]
AID - gutjnl-2016-313316 [pii]
AID - 10.1136/gutjnl-2016-313316 [doi]
PST - ppublish
SO  - Gut. 2018 Feb;67(2):271-283. doi: 10.1136/gutjnl-2016-313316. Epub 2017 Apr 4.