Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial

Abstract

Objective: To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses.

Design: Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period.

Results: Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose.

Conclusion: These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.

Keywords: colonic microflora; glucose metabolism; inflammation; short-chain fatty acids.

Figure 1

The total and molar percentages of acetate, propionate and butyrate measured in stool (A, B) and fasting serum (C, D) following 42 days of cellulose, inulin and inulin-propionate ester (IPE) supplementation. Mean±SEM (n=12). *P<0.05. Data were analysed by repeated measures analysis of variance (ANOVA) with post hoc Fisher’s least significant difference (LSD) tests. SCFA, short-chain fatty acid.

Figure 2

(A) Homeostatic model assessment 2-insulin resistance (HOMA2-IR), (B) Matsuda Insulin Sensitivity Index (ISI), (C) adipose tissue insulin resistance (AT-IR) and (D) fasting insulin following 42 days of cellulose, inulin and inulin-propionate ester (IPE) supplementation. Each individual symbol represents a volunteer and lines represent mean±SEM (n=12). *P<0.05; **P<0.01. (A) and (D) were analysed by repeated measures analysis of variance (ANOVA) with post hoc Fisher’s least significant difference (LSD) tests. (B) and (C) were analysed by Friedman test and post hoc Wilcoxon signed-rank test.

Figure 3

(A) The proportion of CD4⁺ Treg and (B) Th17 cells, (C) the ratio of Treg:Th17, (D) the proportion of CD19⁺ B cells, (E) interferon gamma (IFNγ) T cell spot forming cell response to the cytomegalovirus/Epstein-Barr virus/flu (CMV/EBV/flu [CEF]) peptide pool, and (F) IFNγ T cell spot forming cell response to the Pseudomonas aeruginosa antigen, OprF, following 42 days of cellulose, inulin and inulin-propionate ester (IPE) supplementation. Each individual symbol represents a volunteer and lines represent mean±SEM (n=12). (A) and (E) were analysed by repeated measures analysis of variance (ANOVA). (B), (C), (D) and (F) were analysed by Friedman test. sfc, spot forming cell.

Figure 4

(A) IgG and (B) IL-8 in fasting serum following 42 days of cellulose, inulin and inulin-propionate ester (IPE) supplementation. Each individual symbol represents a volunteer and lines represent mean±SEM (n=12). (C) IL-8 release from peripheral blood mononuclear cells (PBMC) isolated from 12 healthy volunteers cultured for 48 with 4 mM sodium chloride, 4 mM sodium acetate and 4 mM sodium propionate. The concentration of IL-8 produced following culture with media alone was subtracted from the treated samples to determine change in IL-8. Mean±SEM (n=12). *P<0.05; **P<0.01. (A) was analysed by repeated measures analysis of variance (ANOVA) with post hoc Fisher’s least significant difference (LSD) tests. (B) and (C) were analysed by Friedman test and post hoc Wilcoxon signed-rank test. IL-8, interleukin-8.