Abstract/Summary

The purpose of this project was to develop a novel blend of prebiotics with the potential to influence perceptions of satiety and thus food intake. Prebiotics beneficially modulate the composition of the gut microbiota, they are fermented primarily in the ceacum resulting in the production of metabolites, including acetate and propionate. These metabolites are thought to impact appetite regulation by acting as a ligand, with a high affinity to G-coupled receptors (GPR42/3) located on L-cells, throughout the length of the colon. A subsequent stimulation of circulating satiety hormones triggers anorexogenic pathways involved in reducing food intake and increasing satiety. It is therefore hypothesised that using blends of prebiotics to increase SCFA production along the length of the colon might be of benefit in weight management. Initially a literature review is presented, evaluating dietary intervention studies that have explored the satiety inducing effects of different prebiotics/prebiotic candidates on various human populations. In the reviewed 17/27 intervention studies prebiotics were associated with increased satiety. Variations in study design, dose and study food matrix might explain the disparity in the results. The work of screening eleven commonly consumed prebiotics/prebiotic candidates for their fermentation characteristics is described in the first experimental chapter. Using an in vitro batch culture model of the gut (n=3), those prebiotics that stimulated the growth of acetate and propionate producing bacterial species, such as Bifidobacterium and Propionibacterium specifically at later fermentation time points (24-48h) (indicating a slower fermentation), were considered for further study. Inulin was identified as the most bifidogenic of all the substrates. Three substrates that performed well in the first experimental section were blended with inulin to produce 3 novel prebiotic blends (inulin + resistant starch, inulin + α-gluco-oligosaccharides, and inulin + arabinoxylan). The fermentation characteristics of these blends were assessed in depth using a 3-stage continuous culture colonic model (n=3). The focus was on the influence of these prebiotic blends on the third fermentation vessel, which simulates the distal region of the colon. The hypothesis that residual prebiotic activity in this vessel might be associated with a flatter and more sustained SCFA spike following consumption, and that this might lead to better appetite control. Of the 3 blends, I+RS and I+ABX outperformed I+GLOS exhibiting a sustained fermentation towards V3, however I+ABX was the frontrunner, due to the levels of propionate produced, including those in V3, which was desirable. In a 9-week crossover, placebo controlled and double blinded human appetite study. I+ABX was consumed daily by healthy weight men. The primary endpoint was satiety and ad libitum energy intake on a study visit day. Secondary endpoints were prebiotic effects assessed in stool and urine. Subjective satiety scores were not influenced however there was a statistically significant reduction in energy intake during the ad libitum lunch of 34.28Kcal. If extended over three meals this might equate to a <100 Kcal reduction in energy intake per day, more than sufficient to elicit progressive weight loss or to contribute to weight maintenance. The intervention also induced significant increases in the abundance of Bifidobacterium (P=0.017) and Propionibacterium (P=0.021) in stool samples and an increase in the concentration of acetate. This research has demonstrated a pipeline for the development of prebiotics with the potential for use in weight management products. Chronic consumption of LC-FOS with ABX significantly reduced food intake and therefore supplementation of the diet with I+ABX may be a useful tool in weight management. Further work is needed to understand the mechanism and to establish additional prebiotic benefits associated with consuming this blend. Our blended product is being patented by our industrial sponsor and may be explored in further clinical intervention study over extended time frames with weight control as the endpoint.