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

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Gut microbiota
Original article
Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction
  1. Emilie Catry1,
  2. Laure B Bindels1,
  3. Anne Tailleux2,3,4,5,
  4. Sophie Lestavel2,3,4,5,
  5. Audrey M Neyrinck1,
  6. Jean-François Goossens6,7,
  7. Irina Lobysheva8,
  8. Hubert Plovier1,9,
  9. Ahmed Essaghir10,
  10. Jean-Baptiste Demoulin10,
  11. Caroline Bouzin11,
  12. Barbara D Pachikian1,
  13. Patrice D Cani1,9,
  14. Bart Staels2,3,4,5,
  15. Chantal Dessy8,
  16. Nathalie M Delzenne1
  1. 1 Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium
  2. 2 European Genomic Institute for Diabetes (EGID), Univ Lille, Lille, France
  3. 3 INSERM UMR 1011, Lille, France
  4. 4 Institut Pasteur de Lille, Lille, France
  5. 5 CHU de Lille, Lille, France
  6. 6 Centre Universitaire de Mesures et d'Analyses, Univ. Lille, Lille, France
  7. 7 EA 7365 GRITA, Lille, France
  8. 8 Pole of Pharmacology and Therapeutics, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
  9. 9 Walloon Excellence in Life sciences and BIOtechnology (WELBIO), Belgium
  10. 10 Pole of Experimental Medicine, de Duve Institute, Université catholique de Louvain, Brussels, Belgium
  11. 11 IREC Imaging Platform, Université catholique de Louvain, Brussels, Belgium
  1. Correspondence to Professor Nathalie M Delzenne, Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, 73, avenue E. Mounier, B01.73.11, Brussels 1200, Belgium; nathalie.delzenne{at}uclouvain.be

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.

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

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/gutjnl-2016-313316

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    Footnotes

    • CD and NMD contributed equally.

    • Twitter Follow Patrice Cani @MicrObesity

    • Contributors Conceptualisation: EC, CD and NMD; Methodology: EC, CD and NMD; Investigation: EC, LBB, AT, SL, AMN, IL, CB, PDC and BS; Formal analysis: J-FG, HP, AE and J-BD; Writing-original draft: EC, CD and NMD; Writing review and editing: all the authors; Supervision: CD and NMD.

    • Funding This work is supported by FNRS (Fond National de la Recherche Scientifique, Belgium; CDR J.0122.15). LBB was a postdoctoral researcher from the FRS-FNRS and is the recipient of subsidies from the FSR (Fonds Spéciaux de la Recherche, UCL). HP is a research fellow at the FRS-FNRS. NMD is a recipient of grants from FRS-FNRS, from Wallonia supported by the competitive cluster Wagralim (ADIPOSTOP project, convention 7366; FOOD4GUT project, convention 1318148) and from the European Union's Seventh Framework Program (grant agreement no 613979). PDC is a research associate at the FRS-FNRS and the recipient of grants from FNRS (convention J.0084.15, convention 3.4579.11), PDC (Projet de Recherche, convention: T.0138.14), WELBIO-CR-2012S-02R, the Funds Baillet Latour (Grant for Medical Research 2015). PDC is a recipient of an ERC Starting Grant 2013 (starting grant 336452-ENIGMO). CD is a senior research associate at FRS-FNRS. BS is a recipient of the Institut Universitaire de France. This work was partly supported by grants from the European Genomic Institute for Diabetes (ANR-10-LABX-46) and the ERC Grant (Immunobile, contract 694717).

    • Competing interests None declared.

    • Ethics approval The experiments were approved by and performed in accordance with the guidelines of the local ethics committee. Housing conditions were as specified by the Belgian Law of 29 May 2013, regarding the protection of laboratory animals (agreement no LA1230314).

    • Provenance and peer review Not commissioned; externally peer reviewed.

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