Demonstration of a Novel Approach in the Management of Endothelial Dysfunction

Gut. 2017 Jun 28. pii: gutjnl-2017-314012. doi: 10.1136/gutjnl-2017-314012. [Epub ahead of print] Endothelial dysfunction: what is the role of the microbiota? Zoetendal EG1, Smidt H1. Author information 1Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands.In this issue, Catry et al described a study in which inulin-type fructans (ITF) improved endothelial dysfunction in mice.1 They demonstrated that the supplementation of ITF reverses endothelial dysfunction in mesenteric and carotid arteries of apolipoprotein E (apoE) gene knockout mice that were fed an n-3 polyunsaturated fatty acid-depleted diet. They further showed that improvement of endothelial dysfunction was accompanied with a change in microbiota composition and key gut peptides. Endothelial dysfunction is a pathological state of the inner lining of the blood vessels which is characterised by a reduction in vasodilation in response to endothelial stimuli and considered an early key marker of cardiovascular disease.2 Impaired synthesis and release of nitric oxide (NO) by the endothelium is considered one of the important mechanisms associated with endothelial dysfunction. A wide variety of risk factors associated with cardiovascular disease have been identified. These include general lifestyle factors such as the typical ‘Western diet’ and smoking, but also disorders, such as metabolic syndrome and type 2 diabetes as well as chronic inflammation. Increasing evidence indicates that the intestinal microbiota plays a key role in the latter risk factors for cardiovascular disease. A recent study demonstrated … KEYWORDS: intestinal microbiology; ribosomal RNA ​ 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 novelapproach 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 1Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.2European Genomic Institute for Diabetes (EGID), Univ Lille, Lille, France.3INSERM UMR 1011, Lille, France.4Institut Pasteur de Lille, Lille, France.5CHU de Lille, Lille, France.6Centre Universitaire de Mesures et d’Analyses, Univ. Lille, Lille, France.7EA 7365 GRITA, Lille, France.8Pole of Pharmacology and Therapeutics, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium.9Walloon Excellence in Life sciences and BIOtechnology (WELBIO), Belgium.10Pole of Experimental Medicine, de Duve Institute, Université catholique de Louvain, Brussels, Belgium.11IREC 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 gutmicrobiota 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. CLICK HERE TO VIEW FULL-TEXT ​ Endothelial Function Scientific Update Sponsored by Endothelix Inc. www.endothelix.com

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