Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction
Open accessAbstract
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.
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Professionals describe a lack in their own knowledge or a limited understanding of precision medicine.
“Professionals also describe a lack in their own knowledge or a limited understanding, as quantitative studies demonstrate [36, 37, 44, 81, 82, 92, 103, 104].”
From Patients’ and professionals’ views related to ethical issues in precision medicine: a mixed research synthesis (2021) · cites this paper as [36]
The Introduction and Discussion address dietary inulin-type fructans and endothelial dysfunction in mice, not professionals’ understanding of precision medicine. Searches for professionals’ knowledge, precision medicine, and related survey findings found no passage addressing the claim; page numbers were not available in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredIn Apoe−/− mice on an n-3 PUFA-depleted diet, supplementation of dietary inulin-type fructans reversed endothelial dysfunction in carotid arteries via activation of the NO synthase/NO pathway.
“In a different mouse model involving Apoe E−/− mice on a n-3 polyunsaturated fatty acid (PUFA)-depleted diet for 12 weeks, supplementation of dietary inulin-type fructans were shown to reverse endothelial dysfunction in carotid arteries via activation of the nitric oxide (NO) synthase/NO pathway169.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [169]
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- Authors
- Catry, E., Bindels, L. B., Tailleux, A., Lestavel, S., Neyrinck, A. M., Goossens, J.-F., Lobysheva, I., Plovier, H., Essaghir, A., Demoulin, J.-B., Bouzin, C., Pachikian, B. D., Cani, P. D., Staels, B., Dessy, C., & Delzenne, N. M.
- Affiliations
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium
- UCLouvain (BE)
- Inserm (FR)
- Université de Lille (FR)
- Walloon Excellence in Lifesciences and Biotechnology (BE)
- de Duve Institute (BE)
- Corresponding author
- Delzenne, Nathalie M
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2017-04-04
- Volume
- 67
- Issue
- 2
- Pages
- 271-283
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC5868295
- OpenAlex
- W2604952437
- Cited by
- 194
- References
- 56
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 15 · 2023: 19 · 2022: 34 · 2021: 25 · 2020: 27 · 2019: 22 · 2018: 19 · 2017: 10
- FWCI
- 17.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Gut (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- DIAL (Catholic University of Leuven) (submittedVersion, other-oa)
- LillOA (Université de Lille (University Of Lille)) (submittedVersion, other-oa)
- LillOA (Université de Lille (University Of Lille)) (submittedVersion, cc-by)
- HighWire Press Open Archive (submittedVersion)
- Funders
- European Genomic Institute for Diabetes (ANR-10-LABX-46)
- European Commission (613979, 694717, ANR-10-LABX-46)
- Agence Nationale de la Recherche (ANR‐10‐LABX‐46, 10-LABX-46, ANR-10-LABX-0046, ANR-10, ANR-10-LABX)
- Fonds De La Recherche Scientifique - FNRS (J.0084.15, WELBIO-CR-2012S-02R, T.0138.14, CDR J.0122.15, 3.4579.11)
- Institut Universitaire de France
- Walloon excellence in life sciences and biotechnology
- FP7 Ideas: European Research Council (336452)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Microbial Metabolites in Food Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- inulin-type fructans, prebiotics, endothelial dysfunction, gut microbiota, ApoE-deficient mice, hepatic steatosis, Akkermansia, bile acids, glucagon-like peptide-1, carotid artery, mesenteric arteries, cardiovascular disease prevention
- MeSH terms
- Gastrointestinal Microbiome, Mice, Knockout, ApoE, Aminopeptidases, Animals, Bacteria, Bile Acids and Salts, Carotid Arteries, Cecum, Disease Models, Animal, Endothelium, Vascular, Fructans, Male, Mesenteric Arteries, Mice, Inbred C57BL, Neurotensin, Nitric Oxide, Vasodilation, Fatty Acids, Omega-3, Gene Expression, Nitric Oxide Synthase, Dietary Supplements, Antimicrobial Cationic Peptides, Symporters, Organic Anion Transporters, Sodium-Dependent, Mice, Glucagon-Like Peptide 1, Proglucagon, Prebiotics
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