Dietary N-acylethanolamines are bioaccessible in the small intestine and modulate postprandial hormonal responses: a randomized crossover trial in subjects with ileostomy

Abstract

N-acylethanolamines (NAEs) are bioactive lipid mediators involved in the regulation of appetite, inflammation, and gut-brain signaling. This study investigated the metabolic fate of dietary NAEs following the consumption of two test meals with differing NAE content in subjects with ileostomy, and evaluated their effects on gastrointestinal hormones, glycaemia, and appetite regulation. An acute, double-blind, randomized, crossover postprandial study was conducted in ileostomy patients who consumed either a high-NAE meal (HNM) or a low-NAE meal (LNM) on two separate occasions. Ileal fluid and plasma samples were collected over an 8-hour postprandial period for analysis of NAEs and endocannabinoids (ECs). Baseline ileal microbiota composition was assessed. At the end of the 8-hour period, participants completed a buffet meal test to evaluate ad libitum energy intake. Dietary NAEs were significantly recovered in ileal fluids after HNM intake, with concentrations approximately 3-fold higher than after LNM, suggesting partial digestion and release from the food matrix. No significant differences in postprandial plasma NAE concentrations were observed between meals. HNM consumption led to higher postprandial levels of plasma insulin, C-peptide, and glucose-dependent insulinotropic polypeptide, despite no differences in glycemic response or subsequent ad libitum energy intake. Metagenomic analysis identified clusters of ileal microbial taxa associated with circulating lipid profiles, suggesting a role of the small intestinal microbiota in the metabolism of NAEs and ECs. Dietary NAEs reach the small intestine at active concentrations and may influence local signaling via GPR119, with microbiota composition influencing their release from food.