ObjectiveThe colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults.DesignTo investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults.ResultsPropionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group.ConclusionsThese data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans.Trial registration numberNCT00750438.

Exercise studies have suggested that the presence of carbohydrate in the human mouth activates regions of the brain that can enhance exercise performance but direct evidence of such a mechanism is limited. The first aim of the present study was to observe how rinsing the mouth with solutions containing glucose and maltodextrin, disguised with artificial sweetener, would affect exercise performance. The second aim was to use functional magnetic resonance imaging (f MRI) to identify the brain regions activated by these substances. In Study 1A, eight endurance-trained cyclists (V O 2 max 60.8 ± 4.1 ml kg −1 min −1 ) completed a cycle time trial (total work = 914 ± 29 kJ) significantly faster when rinsing their mouths with a 6.4% glucose solution compared with a placebo containing saccharin (60.4 ± 3.7 and 61.6 ± 3.8 min, respectively, P = 0.007). The corresponding f MRI study (Study 1B) revealed that oral exposure to glucose activated reward-related brain regions, including the anterior cingulate cortex and striatum, which were unresponsive to saccharin. In Study 2A, eight endurance-trained cyclists (V O 2 max 57.8 ± 3.2 ml kg −1 min −1 ) tested the effect of rinsing with a 6.4% maltodextrin solution on exercise performance, showing it to significantly reduce the time to complete the cycle time trial (total work = 837 ± 68 kJ) compared to an artificially sweetened placebo (62.6 ± 4.7 and 64.6 ± 4.9 min, respectively, P = 0.012). The second neuroimaging study (Study 2B) compared the cortical response to oral maltodextrin and glucose, revealing a similar pattern of brain activation in response to the two carbohydrate solutions, including areas of the insula/frontal operculum, orbitofrontal cortex and striatum. The results suggest that the improvement in exercise performance that is observed when carbohydrate is present in the mouth may be due to the activation of brain regions believed to be involved in reward and motor control. The findings also suggest that there may be a class of so far unidentified oral receptors that respond to carbohydrate independently of those for sweetness.

Over the last 20 years there has been an increasing interest in the influence of the gastrointestinal tract on appetite regulation. Much of the focus has been on the neuronal and hormonal relationship between the gastrointestinal tract and the brain. There is now mounting evidence that the colonic microbiota and their metabolic activity have a significant role in energy homeostasis. The supply of substrate to the colonic microbiota has a major impact on the microbial population and the metabolites they produce, particularly short chain fatty acids (SCFAs). SCFAs are produced when non-digestible carbohydrates, namely dietary fibres and resistant starch, undergo fermentation by the colonic microbiota. Both the consumption of fermentable carbohydrates and the administration of SCFAs have been reported to result in a wide range of health benefits including improvements in body composition, glucose homeostasis, blood lipid profiles and reduced body weight and colon cancer risk. However, published studies tend to report the effects that fermentable carbohydrates and SCFAs have on specific tissues and metabolic processes, and fail to explain how these local effects translate into systemic effects and the mitigation of disease risk. Moreover, studies tend to investigate SCFAs collectively and neglect to report the effects associated with individual SCFAs. Here, we bring together the recent evidence and suggest an overarching model for the effects of SCFAs on one of their beneficial aspects: appetite regulation and energy homeostasis.

Purpose of this ReviewThis review assesses the latest evidence linking short-chain fatty acids (SCFA) with host metabolic health and cardiovascular disease (CVD) risk and presents the latest evidence on possible biological mechanisms.Recent FindingsSCFA have a range of effects locally in the gut and at both splanchnic and peripheral tissues which together appear to induce improved metabolic regulation and have direct and indirect effects on markers of CVD risk.SummarySCFA produced primarily from the microbial fermentation of dietary fibre appear to be key mediators of the beneficial effects elicited by the gut microbiome. Not only does dietary fibre fermentation regulate microbial activity in the gut, SCFA also directly modulate host health through a range of tissue-specific mechanisms related to gut barrier function, glucose homeostasis, immunomodulation, appetite regulation and obesity. With the increasing burden of obesity worldwide, the role for gut microbiota-generated SCFA in protecting against the effects of energy dense diets offers an intriguing new avenue for regulating metabolic health and CVD risk.