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.

Edward S Chambers, Claire S Byrne, Douglas J Morrison, Kevin G Murphy, Tom Preston, Catriona Tedford, Isabel Garcia-Perez, Sofia Fountana, Jose Ivan Serrano-Contreras, Elaine Holmes, Catherine J Reynolds, Jordie F Roberts, Rosemary J Boyton, Daniel M Altmann, Julie A K McDonald, Julian R Marchesi, Arne N Akbar, Natalie E Riddell, Gareth A Wallis, Gary S Frost

Journal: Gut 2019;68(8):1430-1438

PMID: 30971437

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Plain Language Summary

Literature shows that higher intakes of dietary fibre are associated with a reduced risk of type 2 diabetes. The main aim of this study was to elucidate the underlying mechanisms behind improvements in glucose homeostasis following long-term delivery of propionate (a short-chain fatty acid produced by human gut microbiota in response to dietary fibre) to the human colon. The study is a randomised, double-blind, placebo-controlled cross over trial. Fourteen participants randomly received 20 g/day of a low-fermentable fibre control, a high-fermentable fibre control and inulin-propionate ester (IPE) for 42 days each. Results indicate that stool concentrations of short-chain fatty acids were not different following the three supplementation periods. Furthermore, dietary supplementation with 20 g/day IPE promoted no superior impacts on measures of glucose homeostasis compared with inulin (high-fermentable fibre), yet both IPE and inulin improved insulin resistance relative to cellulose (low-fermentable fibre). Authors conclude that manipulating the colonic fermentation profile of a dietary fibre in favour of propionate promotes selective effects on the mechanisms that contribute to metabolic dysregulation.

Abstract

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.

Address: Section for Nutrition Research, Department of Medicine, Imperial College London, London, UK.; Stable Isotope Biochemistry Laboratory, Scottish Universities Environmental Research Centre, Glasgow, UK.; Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK.; School of Computing, Engineering and Physical Sciences, University of the West of Scotland, Paisley, UK.; Computational and Systems Medicine, Imperial College London, London, UK.; Department of Medicine, Imperial College London, London, UK.; Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Imperial College London, London, UK.; Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Imperial College London, London, UK.; School of Biosciences, University of Cardiff, Cardiff, UK.; Division of Infectionand Immunity, University College London, London, UK.; Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.; School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.

DOI: 10.1136/gutjnl-2019-318424

Patient Centred Factor

Triggers: Obesity/inulin

Clinical Imbalances

Hormonal Gastro-intestinal

Laboratory Testing

Blood Stool

Modifiable Lifestyle Factors

Diet

Jadad Score

Allocation Concealment

Yes

Nutrition Evidence Keywords

Insulin resistance BMI Obesity Overweight Physical activity Glucose Insulin Body mass index Gut microbiota Metabolic disease Type 2 diabetes Glycaemic Insulin sensitivity Adipose tissue Short-chain fatty acid

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MeSH Terms: Adult, Body Mass Index, Cross-Over Studies, Dietary Supplements, Double-Blind Method, Feces, Female, Gastrointestinal Microbiome, Humans, Inflammation, Insulin, Insulin Resistance, Inulin, Male, Metabolome, Middle Aged, Obesity, Overweight, Propionates, Treatment Outcome