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

Abstract

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 CO2 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.

Figure 1

Mean (S.E.M.) absolute SCFA production (A), molar ratios (B), efficiency and yield of propionate (C) and efficiency and solubility (D) from IPE with propionate content ranging from 0 to 61 wt% in faecal fermentations (n = 3). Treatments were compared, for each SCFA, using anova and significant differences from inulin control (a, P < 0.05) and IPE d_e = 1.0 (b, P < 0.05) are indicated. A polynomial fit was used to model the solubility vs. degree of esterification data with the following equation: y = 0.045x ³−0.32x ² + 0.554x + 0.02, R ² = 1.

Figure 2

Profile of ¹³ CO ₂ recovery (a) and mean (s.d.) cumulative ¹³C recovery (b) from propionate release and oxidation following supplementation with the IPE‐27 and IPE‐54. Breath ¹³ CO₂ excretion for IPE‐27 was higher (from 1 h onwards) compared with IPE‐54 (P < 0.05). IPE‐27 led to significantly greater ¹³C recovery in breath CO ₂ (64.9 vs. 24.9%, P = 0.001) compared with IPE‐54.

Figure 3

Mean (s.d.) total energy intake (a; kcal) and ad libitum buffet meal energy intake (b; kcal) during the experimental day following 7‐day supplementation with IPE‐27, IPE‐54 or inulin. IPE‐27 led to significantly lower total energy intake compared with IPE‐54 (1167.6 vs. 1432.9 kcal, *P = 0.016) but only a trend towards lower intake compared with inulin control (1167.6 vs. 1444.6 kcal, P = 0.076). IPE‐27 led to a significant 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). IPE‐54 was not significantly different from inulin control.