Demonstration of a novel approach in the management of endothelial dysfunction

 

Gut. 2017 Apr 4. pii: gutjnl-2016-313316. doi: 10.1136/gutjnl-2016-313316. [Epub ahead of print]

Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction.

Catry E1, Bindels LB1, Tailleux A2,3,4,5, Lestavel S2,3,4,5, Neyrinck AM1, Goossens JF6,7, Lobysheva I8, Plovier H1,9, Essaghir A10, Demoulin JB10, Bouzin C11, Pachikian BD1, Cani PD1,9, Staels B2,3,4,5, Dessy C8, Delzenne NM1.

Author information

1
Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
2
European Genomic Institute for Diabetes (EGID), Univ Lille, Lille, France.
3
INSERM UMR 1011, Lille, France.
4
Institut Pasteur de Lille, Lille, France.
5
CHU de Lille, Lille, France.
6
Centre Universitaire de Mesures et d’Analyses, Univ. Lille, Lille, France.
7
EA 7365 GRITA, Lille, France.
8
Pole of Pharmacology and Therapeutics, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium.
9
Walloon Excellence in Life sciences and BIOtechnology (WELBIO), Belgium.
10
Pole of Experimental Medicine, de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
11
IREC Imaging Platform, Université catholique de Louvain, Brussels, Belgium.

Abstract

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.

KEYWORDS:

BILE ACID METABOLISM; CARDIOVASCULAR DISEASE; ENDOCRINE HORMONES; INTESTINAL MICROBIOLOGY; PREBIOTIC


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