Diet shapes the metabolite profile in the intact human ileum which impacts PYY release
Description
The human ileum contains a high density of enteroendocrine L-cells which release the appetite supressing hormones Glucagon-like peptide-1 (GLP-1) and Peptide Tyrosine Tyrosine (PYY) in response to food intake. Recent evidence highlighted the potential role of food structures in PYY release but the link between ileal metabolites and appetite hormone release remains unclear owing to access issues to intact human ileum. In a randomised crossover trial (ISRCTN11327221; isrctn.com), we investigated the role of human ileum in GLP-1 and PYY release by giving healthy volunteers diets differing in fibre and food structure: high-fibre (intact or disrupted food structures) or low-fibre disrupted food structures. We used nasoenteric tubes to sample chyme from the intact distal ileum lumen of humans in fasted state and every 60 min for 480 min postprandially. We demonstrate the highly dynamic, wide-ranging molecular environment of the ileum over time, with a drop of almost three quarters (73.6%) in ileum bacterial numbers along with a drop in bacterial metabolites after food intake. We also show that high fibre diets, independent of food structure, increased PYY release compared to a low-fibre diet during 0-240 min postprandially. High-fibre diets also increased ileal stachyose and a disrupted high-fibre diet increased certain ileal amino acids. Treatment of human ileal organoids with ileal fluids or an amino acid and stachyose mixture stimulated PYY expression in a similar profile to blood PYY concentrations, confirming the role of ileal metabolites in PYY release. Our study demonstrates the diet-induced changes over time in the metabolite environment of intact human ileum which play a role in PYY release.