Randomised clinical study: inulin short‐chain fatty acid esters for targeted delivery of short‐chain fatty acids to the human colon

BACKGROUND: Short‐chain fatty acids (SCFA) produced through fermentation of nondigestible carbohydrates by the gut microbiota are associated with positive metabolic effects. However, well‐controlled trials are limited in humans. AIMS: To develop a methodology to deliver SCFA directly to the colon, and to optimise colonic propionate delivery in humans, to determine its role in appetite regulation and food intake. METHODS: Inulin SCFA esters were developed and tested as site‐specific delivery vehicles for SCFA to the proximal colon. Inulin propionate esters containing 0–61 wt% (IPE‐0–IPE‐61) propionate were assessed in vitro using batch faecal fermentations. In a randomised, controlled, crossover study, with inulin as control, ad libitum food intake (kcal) was compared after 7 days on IPE‐27 or IPE‐54 (10 g/day all treatments). Propionate release was determined using (13)C‐labelled IPE variants. RESULTS: In vitro, IPE‐27–IPE‐54 wt% propionate resulted in a sevenfold increase in propionate production compared with inulin (P < 0.05). In vivo, IPE‐27 led to greater (13)C recovery in breath CO (2) than IPE‐54 (64.9 vs. 24.9%, P = 0.001). IPE‐27 also led to a reduction in energy intake during the ad libitum test meal compared with both inulin (439.5 vs. 703.9 kcal, P = 0.025) and IPE‐54 (439.5 vs. 659.3 kcal, P = 0.025), whereas IPE‐54 was not significantly different from inulin control. CONCLUSIONS: IPE‐27 significantly reduced food intake suggesting colonic propionate plays a role in appetite regulation. Inulin short‐chain fatty acid esters provide a novel tool for probing the diet–gut microbiome–host metabolism axis in humans.