Title: Increase colonic propionate as a method of preventing weight gain in young adults
Funder: Department of Health and Social Care

Abstract: Background: A major public health challenge is the development of effective strategies to prevent the weight gain that occurs throughout adult life at a population level. Young adults (25-35 years) experience the fastest weight gain of approximately 7-10kg over 10 years which is associated with a number of chronic diseases(1).The gradual long-term weight gain observed in adults can be explained by a small habitual positive energy balance of 50 kcal/day (2). Short chain fatty acids (SCFA) are molecules produced by the fermentation of non-digestible carbohydrates (NDCs) by the gut microbiota in the colon (3). Recent evidence suggests that SCFA act through free fatty acid receptors (FFAR2) on enteroendocrine cells chiefly in the colon to stimulate release of the anorexic gut hormones peptide YY (PYY) and glucagon like peptide –1 (GLP-1)(4). To predictably increase colonic SCFA release we have developed a colonic novel delivery vehicle inulin-propionate ester (IPE). We have conducted the first studies in man, demonstrating significant appetite suppression and increased plasma PYY and GLP-1 concentrations with IPE and have also completed a 24-week human intervention study which demonstrated significantly lower weight gain in overweight people compared with control subjects (5). In addition, our recent pilot data demonstrated that a one week supplementation period with IPE significantly increases fasting and postprandial energy expenditure by 7%. Hypothesis: IPE supplementation will prevent weight gain compared with inulin control in young adults at higher risk of weight gain. Design: A randomised, placebo-controlled double-blind study to investigate the impact of IPE on weight gain prevention. Cohort: Male and female adults, 20-35 years, BMI 25-30 kg/m2 Environment: NIHR/Wellcome Trust Imperial CRF at Imperial College London and the Glasgow Biomedicine CRF at University of Glasgow. Interventions: IPE vs control (inulin). The IPE and control will be given to participants in 10g sachets and they will be instructed to take one sachet per day with their normal diet for 12 months. Outcomes: The primary outcome measure will be weight gain at 12 months. Weight will be measured at 0,2,6 and 12 months. Secondary outcomes will include assessments of physiological variables underpinning the improvements in body weight maintenance, including colonic metabolism, appetite regulation, energy expenditure and lipid oxidation. Sample size: The proof of concept trial provided a difference between arms of 1.4kg (95% CI:(-0.3 to 3.1). This indicates 95% support for an underlying positive intervention effect. The enrichment of the cohort with young adults at risk of weight gain would allow 2kg effect size to be detected with 90% power, 5% significance level, SD 4.35kg, by randomising 270 participants, with 75% retention. A substudy (N=52) will provide in-depth data on energy expenditure, calorimetry, appetite regulation, breath hydrogen at oxidation and gut microbiota. Statistical analysis: The primary outcome of weight gain at 12 months will be compared between the two groups using an intention-to-treat approach and a linear mixed effect model and sensitivity analysis for missing data. The main impact of this study will be a methodology to prevent weight gain at a population level. This has potential to make a major public health impact given the increased risk of diabetes, coronary heart disease and cancer that occurs with the accumulation of weight gain

Lay abstract: Being overweight is associated with many illnesses. In adults, most weight gain occurs when people are in their 20s and 30s and leads to many adults becoming obese by the time they are middle-aged, leading to increased risk of developing diabetes, heart disease and cancer. There is increasing evidence that diet plays an important role in preventing obesity. The amount of fibre (found in edible plant foods such as cereals, fruits, vegetables, dried peas, nuts, lentils and grains) eaten in the diet has been linked to body weight. People who eat low amounts of dietary fibre are more likely to gain weight. Dietary fibre is the major food for the bacteria that live in our gut. We know that dietary fibre keeps the bugs in our gut healthy. The bugs break down dietary fibre to chemicals which can reduce appetite and body fat. We have been working on understanding how these chemicals have this effect. What are we assessing? We have developed a method of delivering these chemicals that are made by the gut bugs by mouth to reduce appetite and weight gain. We have focused on one chemical called propionate because it appears to be the most powerful at reducing appetite. This new food ingredient is call inulin propionate ester (IPE) and it simply delivers the propionate to the right region of the gut where we think it is most effective. We believe that adding IPE to the diet will prevent weight gain in young adults. Design of the study: This study will test the effect of the IPE on weight gain over 12 months. The IPE or a control dietary fibre will be given to 270 volunteers and they will be asked to take this every day over the course of the study. The volunteers will attend study visits at 2, 6 and 12 months after they start to take the IPE or control. The aim of the study will be to see if weight gain is different between the IPE group and the control group after 12 months. The impact of this study will be a new food ingredient which will help to prevent weight gain at a population level. This has potential to make a major impact at a population level which is urgently needed given the increased risk of diabetes, coronary heart disease and cancer that occurs with the accumulation of weight gain.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR;METABOLIC AND ENDOCRINE;ORAL AND GASTROINTESTINAL;STROKE