The effects of 2’-fucosyllactose on acetate production

Clinical trials demonstrated that acute infusion of the gut microbial metabolites short-chain fatty acids (SCFA) to the distal colon beneficially affects human substrate and energy metabolism. Here, we hypothesized that the combination of the human milk oligosaccharide 2’-fucosyllactose (2’-FL) with resistant starch (RS) increases distal colonic SCFA production and improves metabolic parameters in lean men and men with overweight/obesity and prediabetes. In this double-blind, placebo-controlled, randomized, crossover study, 10 lean (BMI 20-24.9 kg/m2) normoglycaemic men and 9 men with prediabetes and overweight/obesity (BMI 25-35 kg/m2) were supplemented with either 2’-FL alone, 2’-FL+RS or placebo one day prior to a clinical investigation day (CID). During the CIDs, blood samples were collected fasted and after consumption of a liquid high-fat mixed meal to determine plasma SCFA acetate, butyrate and propionate concentrations (primary outcomes). Secondary outcomes were fasting and postprandial plasma insulin, glucose, free fatty acid (FFA), glucagon-like peptide-1 and peptide YY concentrations. In addition, fecal SCFA and microbiota composition were determined, and energy expenditure and substrate oxidation (indirect calorimetry) and breath H2 excretion were measured. In lean men, supplementation with 2’-FL increased postprandial plasma acetate (P < .017) and fasting H2 excretion (P < .041) compared to placebo. Postprandial plasma butyrate concentration increased after 2’-FL and 2FL+RS as compared to placebo (P < .05) in lean men and in men with prediabetes and overweight/obesity. Additionally, 2’-FL+RS decreased fasting and postprandial plasma FFA concentrations compared to placebo (P < .05) in lean men, but not in men with prediabetes and overweight/obesity. One-day supplementation of 2’-FL or 2’-FL+RS did not affect fecal SCFA concentrations and microbial composition, glucose homeostasis and satiety hormones, substrate oxidation and energy expenditure in both groups. Supplementation of 2’-FL with or without RS the day prior to investigation increased the concentrations of postprandial butyrate in the systemic circulation in lean men as well as in men with prediabetes and obesity, whilst postprandial acetate was only increased in lean men. The combination of 2’-FL with RS showed a potentially beneficial metabolic effect by lowering plasma FFA in lean men. Future research should investigate the metabolic benefits after prolonged supplementation.