Fiberdia - Effects of prebiotic fibres on gut microbiota, glycaemic control, and appetite in type 2 diabetes
Background: During the last decade, there has been an increasing awareness that the gut microbiota plays a pivotal role in host metabolism and compared to a healthy population, the gut microbiota in type 2 diabetes presents with several unfavourable features that may impair glucose regulation. Prebiotic fibres have shown beneficial effects on gut bacteria, glucometabolic parameters and appetite in non-diabetic individuals.
Aim: to investigate the effect of a prebiotic fibre supplement of inulin-type fructans on fecal microbiota composition and SCFA, postprandial levels of GLP-1 and -2, glucose, insulin, and appetite hormones and subjective measures of appetite in subjects with type 2 diabetes.
Methods: In this double-blinded crossover trial 35 subjects with type 2 diabetes received 16 g inulin-type fructans or a control supplement for 6 weeks in randomized order, with a 4-week wash-out period in between. Before and after each period, we performed a meal tolerance test with measurements of serum/plasma levels of glucose, insulin, GLP-1 and -2, grehlin, PYY and leptin. We also obtained fecal samples for analyses of microbial composition and SCFA.
Results: This first publication from the study provides evidence for increased levels of beneficial bacterial species after six weeks treatment with inulin –type fructans. The findings suggests a moderate potential of these fibres to improve gut microbiota composition and to increase microbial fermentation in type 2 diabetes.
The next two submitted manuscripts present the effect of the prebiotic fibres on GLP-1 and -2, appetite regulating hormones, as well as effects on blood glucose, insulin, and subjective sensation of appetite. A thesis based on these manuscript was submitted UiO for evaluation in October 2020.
Effect of prebiotics on glycaemic control and appetite, and possible pathways. A) Prebiotic fibres escape digestion in the small intestine and B) are fermented into SCFA acids by gut bacteria in the colon. C) The SCFA bind to G-protein coupled receptors in enteroendocrine L-cells. D) This causes increased secretion of GLP-1, GLP-2, and PYY in response to a meal. E) GLP-1 improves regulation of blood glucose by enhancing release of insulin and suppressing release of glucagon from pancreas. GLP-1 also protects the beta-cells. GLP-1 and PYY enhance satiety by affecting the brain and the gastrointestinal system. GLP-2 maintains the intestinal barrier and may thus prevent systemic inflammation. GLP-1 and 2, glucagon-like peptide 1 and 2; PYY, peptide YY; SCFA, short-chain fatty acids. Figure was produced using Servier Medical Art
News from 2021:
Two more papers form the Fiberdia were published in 2021 and MSc Eline Birkeland defended her thesis “The Fiberdia study: Effects of inulin-type fructans on gut microbiota and regulation of blood glucose and appetite in type 2 diabetes - a randomised, placebo-controlled crossover trial” based on the three manuscript from the study, at the University of Oslo in April 2021.
Despite inducing moderate changes in the composition of faecal bacteria, with increased concentrations of bifidobacteria most prominently affected, the prebiotics did not positively affect concentrations of glucose, insulin, gut hormones, appetite ratings or energy intake. Our findings suggest a moderate potential of inulin-type fructans to improve the bacterial composition in the gut and to increase bacterial fermentation in type 2 diabetes. However, the results do not support a role for inulin-type fructans in regulation of blood glucose or appetite in this population.
During 2021 we have initiated collaboration with other researchers to perform post-hoc analyses of serum and feces samples from the Fiberdia:
1) Together with Researcher Cecilie Dahl at the Department of Community Medicine and Global Health at the Institute of Health and Society, University of Oslo, we are investigating whether prebiotic intake increase the uptake of calcium, magnesium and vitamin D, and if this influence bone turnover. Patients with type-2 diabetes have dysbiosis and low-grade inflammation, and they are at high risk of osteoporosis and fractures. Using already collected serum from the Fiberdia trial, we will analyze change in bone turnover markers and uptake of bone-healthy minerals and vitamins (calcium, magnesium and vitamin D) after supplementation with prebiotics. This will be the main object of a Master’s thesis in Clinical Nurtition at the University of Oslo 2022/2023.
2) An Estonian based Biotechnology firm IPDx has developed technology to decode antibody signatures that can be used as biomarkers to detect disease earlier and guide treatment decisions. The aim of this collaboration project is to uncover microbe-IgA relationship by combining 16S rRNA gene sequencing data from Fiberdia and MVA (Mimotope Variation analysis) antibody profiling data from new analyses performed by the IPDx research group. The combination of the 16S sequencing data and MVA data will enable to pinpoint the precise relationship between IgA and microbes in the gut. These analyses will be performed in 2022.
Publications 2021:
1. Birkeland, E., Gharagozlian, S., Birkeland, K. I., Holm, O. K. S., Thorsby, P. M., Aas, A. M. (2021). Effect of inulin-type fructans on appetite in patients with type 2 diabetes: a randomised controlled crossover trial. J Nutr Sci, 10, e72. doi:10.1017/jns.2021.70
2. Birkeland, E., Gharagozlian, S., Gulseth, H. L., Birkeland, K. I., Hartmann, B., Holst, J. J., Holst, R., Aas, A.-M. (2021). Effects of prebiotics on postprandial GLP-1, GLP-2 and glucose regulation in patients with type 2 diabetes: A randomised, double-blind, placebo-controlled crossover trial. Diabetic Medicine, 38(10), e14657. doi:https://doi.org/10.1111/dme.14657
3. Eline Birkeland’s thesis: “The Fiberdia study: Effects of inulin-type fructans on gut microbiota and regulation of blood glucose and appetite in type 2 diabetes: A randomised, placebo-controlled crossover trial https://www.duo.uio.no/bitstream/handle/10852/85692/1/PhD-Birkeland-2021.pdf
Primary Investigator: Anne-Marie Aas, clinical dietitian and associate professor, Oslo University hospital and University of Oslo