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Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction
- Source :
- Gut, Gut, 2018, Gut, 67 (2), pp.271-283. ⟨10.1136/gutjnl-2016-313316⟩, Gut, p. [1-14] (2017), Gut, Vol. 67, no.2, p. 271-283 (2018)
- Publication Year :
- 2018
-
Abstract
- ObjectiveTo 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.DesignWe 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.ResultsITF 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.ConclusionsWe 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.
- Subjects :
- 0301 basic medicine
Apolipoprotein E
Male
Mice, Knockout, ApoE
medicine.medical_treatment
[SDV]Life Sciences [q-bio]
Prebiotic
Gene Expression
Pharmacology
Gut flora
Proglucagon
Aminopeptidases
Intestinal Microbiology
chemistry.chemical_compound
Mice
Feces
Glucagon-Like Peptide 1
Cardiovascular Disease
Endothelial dysfunction
Gut Microbiota
Cecum
Neurotensin
biology
Symporters
Gastroenterology
Inulin
Endocrine Hormones
Bile Acid Metabolism
PREBIOTIC
Mesenteric Arteries
[SDV] Life Sciences [q-bio]
Vasodilation
medicine.anatomical_structure
Carotid Arteries
BILE ACID METABOLISM
Endothelium
Organic Anion Transporters, Sodium-Dependent
CARDIOVASCULAR DISEASE
Nitric Oxide
digestive system
Nitric oxide
Bile Acids and Salts
03 medical and health sciences
Fatty Acids, Omega-3
medicine
Animals
Bacteria
Akkermansia
medicine.disease
biology.organism_classification
Fructans
Gastrointestinal Microbiome
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
Prebiotics
chemistry
Immunology
Dietary Supplements
Endothelium, Vascular
Steatosis
Nitric Oxide Synthase
INTESTINAL MICROBIOLOGY
ENDOCRINE HORMONES
Antimicrobial Cationic Peptides
Subjects
Details
- ISSN :
- 00175749 and 14683288
- Database :
- OpenAIRE
- Journal :
- Gut
- Accession number :
- edsair.doi.dedup.....b913ebb6bd70913668a6e94351cc34a4
- Full Text :
- https://doi.org/10.1136/gutjnl-2016-313316