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Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial
  1. Edward S Chambers1,
  2. Claire S Byrne1,
  3. Douglas J Morrison2,
  4. Kevin G Murphy3,
  5. Tom Preston2,
  6. Catriona Tedford4,
  7. Isabel Garcia-Perez5,
  8. Sofia Fountana5,
  9. Jose Ivan Serrano-Contreras5,
  10. Elaine Holmes5,
  11. Catherine J Reynolds6,
  12. Jordie F Roberts6,
  13. Rosemary J Boyton6,
  14. Daniel M Altmann6,
  15. Julie A K McDonald7,
  16. Julian R Marchesi7,8,
  17. Arne N Akbar9,
  18. Natalie E Riddell10,
  19. Gareth A Wallis11,
  20. Gary S Frost1
  1. 1 Section for Nutrition Research, Department of Medicine, Imperial College London, London, UK
  2. 2 Stable Isotope Biochemistry Laboratory, Scottish Universities Environmental Research Centre, Glasgow, UK
  3. 3 Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK
  4. 4 School of Computing, Engineering and Physical Sciences, University of the West of Scotland, Paisley, UK
  5. 5 Computational and Systems Medicine, Imperial College London, London, UK
  6. 6 Department of Medicine, Imperial College London, London, UK
  7. 7 Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Imperial College London, London, UK
  8. 8 School of Biosciences, University of Cardiff, Cardiff, UK
  9. 9 Division of Infectionand Immunity, University College London, London, UK
  10. 10 Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
  11. 11 School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
  1. Correspondence to Professor Gary S Frost, Section for Nutrition Research, 6th Floor Commonwealth Building Department of Medicine, Imperial College London, London W12 0NN, UK; g.frost{at}


Objective To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses.

Design Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period.

Results Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose.

Conclusion These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.

  • short-chain fatty acids
  • glucose metabolism
  • colonic microflora
  • inflammation

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  • Contributors All authors contributed to writing the manuscript. GSF, DJM, KGM, TP and KT designed the study. DJM, KT and TP produced the inulin-propionate ester. ESC, CSB, GAW, IGP, SF, JISC and EH completed the analysis of metabolic parameters. JFR, CJR, RJB, DMA, ANA and NER completed the inflammatory and immune analysis. JAKM and JRM completed the metataxonomic analysis.

  • Funding This article presents independent research funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC) (BB/L004259/1) and supported by the National Institute of Health Research (NIHR) Clinical Research Facility at Imperial College Healthcare NHS Trust. The Section of Endocrinology and Investigative Medicine is funded by grants from the UK Medical Research Council (MRC) and BBSRC, and is supported by the NIHR Imperial Biomedical Research Centre (BRC) Funding Scheme.

  • Disclaimer The views expressed are those of the authors and not necessarily those of the BBSRC, the NHS, the NIHR or the Department of Health.

  • Competing interests A patent application for ’Compounds and their effects on appetite control and insulin sensitivity' surrounding the use of inulin-propionate ester has been filed by GSF and DJM (WO2014020344). None of the other authors reported a conflict of interest related to the study.

  • Ethics approval London Brent Research Ethics Committee (14/LO/0645)

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

  • Patient consent for publication Not required.

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