Colonic infusions of short-chain fatty acid mixtures promote energy metabolism in overweight/obese men: a randomized crossover trial

Abstract

Short-chain fatty acids (SCFA), formed by microbial fermentation, are believed to be involved in the aetiology of obesity and diabetes. This study investigated the effects of colonic administration of physiologically relevant SCFA mixtures on human substrate and energy metabolism. In this randomized, double-blind, crossover study, twelve normoglycaemic men (BMI 25–35 kg/m2) underwent four investigational days, during which SCFA mixtures (200 mmol/L) high in either acetate (HA), propionate (HP), butyrate (HB) or placebo (PLA) were rectally administered during fasting and postprandial conditions (oral glucose load). Before and for two hours after colonic infusions, indirect calorimetry was performed and blood samples were collected. All three SCFA mixtures increased fasting fat oxidation (P < 0.01), whilst resting energy expenditure increased after HA and HP compared with PLA (P < 0.05). In addition, all three SCFA mixtures increased fasting and postprandial plasma peptide YY (PYY) concentrations, and attenuated fasting free glycerol concentrations versus PLA (P < 0.05). Colonic infusions of SCFA mixtures, in concentrations and ratios reached after fibre intake, increased fat oxidation, energy expenditure and PYY, and decreased lipolysis in overweight/obese men. Human intervention studies are warranted to investigate whether these effects translate into long-term benefits for body weight control and insulin sensitivity in the obese insulin resistant state.

Short-chain fatty acids, prebiotics, synbiotics, and systemic inflammation: a systematic review and meta-analysis

“…Although fasting IL-1b was significantly decreased by the high acetate mixture compared with the high propionate mixture, there was no significant difference compared with placebo or in IL-1b postprandially between treatments (54). Furthermore, changes in other proinflammatory cytokines (TNF-a, IL-6, and IL-8) did not significantly differ between treatments in either the fasting or postprandial conditions (54). The study by van der Beek et al (55) reported lower fasting plasma TNF-a concentrations after distal administration of acetate compared with placebo, however this did not reach significance.…”

“…Acetate is the primary SCFA to enter circulation, and thus has the most potential to exert systemic anti-inflammatory effects (96). In contrast, butyrate is primarily absorbed by colonocytes (96), which may explain why there were no significant changes in inflammation in studies that used butyrate (27,28,54).…”

“…The characteristics of the 5 included SCFA studies are presented in Table 1 (27,28,54,55,76). Canfora et al (54) examined the effect of 3 SCFA mixtures (high acetate, high propionate, and high butyrate), delivered via enema, on systemic inflammation during fasting and postprandial conditions.…”

“…Of the 68 included studies, 5 (7%) used SCFAs (27,28,54,55,76) Table 4). Intervention duration ranged from 1 h to 24 wk (median: 6 wk).…”

Proceedings of the 2017 ASPEN Research Workshop—Gastric Bypass: Role of the Gut

“…This in vivo data confirm the in vitro stimulation of PYY and GLP-1 from a colonic cell line by butyrate and propionate 166 . Colonic infusions of SCFA mixtures, in concentrations and ratios similar to the ones reached after fiber intake, increased fat oxidation, energy expenditure and PYY, and decreased lipolysis in overweight/obese men 172 . The systemic availability and metabolism of colonic-derived SCFAs in healthy subjects has been demonstrated using stable isotopes.…”