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 play 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 have tended 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.

Background: Short-chain fatty acids (SCFAs), metabolites produced through the microbial fermentation of nondigestible dietary components, have key rol

Short‐chain fatty acids (SCFAs), produced from fermentation of dietary fibre by the gut microbiota, have been suggested to modulate energy metabolism. Previous work using rodent models has demonstrated that oral supplementation of the SCFA propionate raises resting energy expenditure (REE) by promoting lipid oxidation. The objective of the present study was to investigate the effects of oral sodium propionate on REE and substrate metabolism in humans. Eighteen healthy volunteers (9 women and 9 men; age 25 ± 1 years; body mass index 24.1 ± 1.2 kg/m ² ) completed 2 study visits following an overnight fast. Tablets containing a total of 6845 mg sodium propionate or 4164 mg sodium chloride were provided over the 180‐minute study period in random order. REE and substrate oxidation were assessed by indirect calorimetry. Oral sodium propionate administration increased REE (0.045 ± 0.020 kcal/min; P = .036); this was accompanied by elevated rates of whole‐body lipid oxidation (0.012 ± 0.006 g/min; P = .048) and was independent of changes in glucose and insulin concentrations. Future studies are warranted to determine whether the acute effects of oral sodium propionate on REE translate into positive improvements in long‐term energy balance in humans.

Supplementation with inulin-propionate ester (IPE), which delivers propionate to the colon, suppresses ad libitum energy intake and stimulates the release of satiety hormones acutely in humans, and prevents weight gain. In order to determine whether IPE remains effective when incorporated into food products (FP), IPE needs to be added to a widely accepted food system. A bread roll and fruit smoothie were produced. Twenty-one healthy overweight and obese humans participated. Participants attended an acclimatisation visit and a control visit where they consumed un-supplemented food products (FP). Participants then consumed supplemented-FP, containing 10 g/d inulin or IPE for six days followed by a post-supplementation visit in a randomised crossover design. On study visits, supplemented-FP were consumed for the seventh time and ad libitum energy intake was assessed 420 min later. Blood samples were collected to assess hormones and metabolites. Resting energy expenditure (REE) was measured using indirect calorimetry. Taste and appearance ratings were similar between FP. Ad libitum energy intake was significantly different between treatments, due to a decreased intake following IPE-FP. These observations were not related to changes in blood hormones and metabolites. There was an increase in REE following IPE-FP. However, this effect was lost after correcting for changes in fat free mass. Our results suggest that IPE suppresses appetite and may alter REE following its incorporation into palatable food products.

The human ileum contains a high density of enteroendocrine L-cells, which release the appetite-suppressing hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) in response to food intake. Recent evidence highlighted the potential role of food structures in PYY release, but the link between food structures, ileal metabolites, and appetite hormone release remains unclear owing to limited access to intact human ileum. In a randomized crossover trial (ISRCTN11327221; isrctn.com ), we investigated the role of human ileum in GLP-1 and PYY release by giving healthy volunteers diets differing in fiber and food structure: high-fiber (intact or disrupted food structures) or low-fiber disrupted food structures. We used nasoenteric tubes to sample chyme from the intact distal ileum lumina of humans in the fasted state and every 60 min for 480 min postprandially. We demonstrate the highly dynamic, wide-ranging molecular environment of the ileum over time, with a substantial decrease in ileum bacterial numbers and bacterial metabolites after food intake. We also show that high-fiber diets, independent of food structure, increased PYY release compared with a low-fiber diet during 0 to 240 min postprandially. High-fiber diets also increased ileal stachyose, and a disrupted high-fiber diet increased certain ileal amino acids. Treatment of human ileal organoids with ileal fluids or an amino acid and stachyose mixture stimulated PYY expression in a similar profile to blood PYY concentrations, confirming the role of ileal metabolites in PYY release. Our study demonstrates the diet-induced changes over time in the metabolite environment of intact human ileum, which play a role in PYY release.

Background. The appetite-regulating effects of non-digestible carbohydrates (NDC) have in part previously been attributed to their effects on intestinal transit rates as well as microbial production of short chain fatty acids (SCFA). Increased colonic production of the SCFA propionate has been shown to reduce energy intake and stimulate gut hormone secretion acutely in humans. Objective. We investigated the effect of the propiogenic NDC, L-rhamnose, on gastrointestinal transit times using a combined ¹³CO₂/H₂ breath test. We hypothesised that L-rhamnose would increase plasma propionate leading to a reduction in appetite, independent of changes in gastrointestinal transit times. Design. We used a dual ¹³C-octanoic acid/lactose ¹³C-ureide breath test combined with breath H₂ to measure intestinal transit times following the consumption of 25 g d⁻¹ L-rhamnose, compared with inulin and cellulose, in 10 healthy humans in a randomised cross-over design pilot study. Gastric emptying (GE) and oro-caecal transit times (OCTTs) were derived from the breath ¹³C data and compared with breath H₂. Plasma SCFA and peptide YY (PYY) were also measured alongside subjective measures of appetite. Results. L-rhamnose significantly slowed GE rates (by 19.5 min) but there was no difference in OCTT between treatments. However, breath H₂ indicated fermentation of L-rhamnose before it reached the caecum. OCTT was highly correlated with breath H₂ for inulin but not for L-rhamnose or cellulose. L-rhamnose consumption significantly increased plasma propionate and PYY but did not significantly reduce subjective appetite measures. Conclusions. The NDCs tested had a minimal effect on intestinal transit time. Our data suggest that L-rhamnose is partially fermented in the small intestine and that breath H₂ reflects the site of gastrointestinal fermentation and is only a reliable marker of OCTT for certain NDCs (e.g. inulin). Future studies should focus on investigating the appetite-suppressing potential of L-rhamnose and verifying the findings in a larger cohort.