Effect of dietary chickpea structures on the small intestine metabolome and microbiome: a randomised crossover trial

The human gastrointestinal tract (GIT) is central to human physiology, yet our understanding of the metabolite, microbial, and hormonal spatiotemporal dynamics in humans is limited. How these environments respond to complex food structures and homeostatic mechanisms they generate is unknown in humans. In this randomised study, ten participants consumed chickpea-based meals with intact versus broken cellular structures, with sampling of oral, gastric, duodenal and ileal fluids. The primary outcome was the postprandial enteroendocrine hormone responses (GIP, GLP-1 and PYY); secondary outcomes were GIT metabolite profiles (¹H NMR) and ileal microbiota (shotgun metagenomics). We observed that food structure markedly altered the spatiotemporal trajectories of metabolites and dominant microbe, driving distinct enteroendocrine hormone responses. Broken-cell meals produced early GIT glucose and maltose peaks associated with rapid GIP responses, whereas intact-cell meals elevated duodenal amino acids and ileal sugars, amino acids and formate, enhancing GLP-1 and PYY responses. Microbial profiles exhibited rapid spatial reorganisation, with evidence that oral bacterial strains transmitted to the ileum, where their abundance was associated with local metabolites and PYY responses. These findings identify food structure as a determinant of postprandial gastrointestinal metabolism and enteroendocrine responses and suggest an underappreciated route for oral bacteria to reach the ileum via the food bolus and impact metabolism. ISRCTN registration: ISRCTN18097249.