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Background: Short-chain fatty acids (SCFAs), metabolites produced through the microbial fermentation of nondigestible dietary components, have key roles in energy homeostasis. Animal research suggests that colon-derived SCFAs modulate feeding behavior via central mechanisms. In humans, increased colonic production of the SCFA propionate acutely reduces energy intake. However, evidence of an effect of colonic propionate on the human brain or reward-based eating behavior is currently unavailable. Objectives: We investigated the effect of increased colonic propionate production on brain anticipatory reward responses during food picture evaluation. We hypothesized that elevated colonic propionate would reduce both reward responses and ad libitum energy intake via stimulation of anorexigenic gut hormone secretion. Design: In a randomized crossover design, 20 healthy nonobese men completed a functional magnetic resonance imaging (fMRI) food picture evaluation task after consumption of control inulin or inulin-propionate ester, a unique dietary compound that selectively augments colonic propionate production. The blood oxygen level–dependent (BOLD) signal was measured in a priori brain regions involved in reward processing, including the caudate, nucleus accumbens, amygdala, anterior insula, and orbitofrontal cortex (n = 18 had analyzable fMRI data). Results: Increasing colonic propionate production reduced BOLD signal during food picture evaluation in the caudate and nucleus accumbens. In the caudate, the reduction in BOLD signal was driven specifically by a lowering of the response to high-energy food. These central effects were partnered with a decrease in subjective appeal of high-energy food pictures and reduced energy intake during an ad libitum meal. These observations were not related to changes in blood peptide YY (PYY), glucagon-like peptide 1 (GLP-1), glucose, or insulin concentrations. Conclusion: Our results suggest that colonic propionate production may play an important role in attenuating reward-based eating behavior via striatal pathways, independent of changes in plasma PYY and GLP-1. This trial was registered at clinicaltrials.gov as NCT00750438.

Fermentable carbohydrates have been shown to exert beneficial effects on dysregulated metabolic conditions such as obesity and diabetes by improving insulin sensitivity and glucose homeostasis, independent of weight loss. Short-chain fatty acids produced by the fermentation of these carbohydrates are considered the primary mediators of these beneficial effects. This thesis aims to evaluate the effect of fermentable carbohydrates on metabolic profiles of pre-diabetic individuals at high risk of developing diabetes and the effect of colonic propionate on glucose and lipid homeostasis in obese individuals. The work presented in this thesis comprises of two axes. The first one is centered on the development and validation of an analytical approach of quantifying SCFAs in human plasma, serum and urine. The applicability of the assay in nutritional studies is also assessed in the second aim. The second part explores the metabolic profiles of pre-diabetic and obese individuals with the employment of 1H nuclear magnetic spectroscopy and mass spectrometry analysis. Concentrations of SCFAs and alteration of the lipid profile were also assessed. The responses to dietary interventions were compared using multivariate statistics. The fermentable carbohydrate inulin increased the production of postprandial SCFAs in pre-diabetic individuals but did not exhibit a significant effect on the overall metabolic profile. Colonic propionate improved the postprandial lipaemia in obese individuals and exerted higher microbial derived metabolites suggesting a role for propionate in the lipid homeostasis in obesity. Propionate levels in the circulation were not affected but systemic acetate significantly increased during the meal test. Finally, the controlled intervention with the non-fermentable carbohydrate cellulose improved lipid profiles in pre-diabetic and obese individuals. Open Access