PT  - JOURNAL ARTICLE
AU  - Emilie Catry
AU  - Laure B Bindels
AU  - Anne Tailleux
AU  - Sophie Lestavel
AU  - Audrey M Neyrinck
AU  - Jean-François Goossens
AU  - Irina Lobysheva
AU  - Hubert Plovier
AU  - Ahmed Essaghir
AU  - Jean-Baptiste Demoulin
AU  - Caroline Bouzin
AU  - Barbara D Pachikian
AU  - Patrice D Cani
AU  - Bart Staels
AU  - Chantal Dessy
AU  - Nathalie M Delzenne
TI  - Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction
AID  - 10.1136/gutjnl-2016-313316
DP  - 2018 Feb 01
TA  - Gut
PG  - 271--283
VI  - 67
IP  - 2
4099  - http://gut.bmj.com/content/67/2/271.short
4100  - http://gut.bmj.com/content/67/2/271.full
SO  - Gut2018 Feb 01; 67
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.