Dietary Modulation of The Human Small Intestine Metabolome and Microbiome

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. Here, we employ naso-enteral intubation to generate a spatiotemporally resolved, multimodal dataset spanning the oral cavity (salivary fluid sampling), stomach, duodenum, and ileum of ten healthy participants. In a randomised trial, participants consumed legume-based meals prepared with varying degrees of structural deconstruction, enabling investigation of how food structure shapes digestive and microbial processes along the small intestine. We find that metabolite profiles and microbial communities exhibit rapid spatial reorganisation, with evidence of transmission of oral bacterial strains to the ileum. The structural properties of food have a major impact on the metabolites and dominant microbe spatiotemporal trajectories, in the GIT thereby influencing the release of gut hormones (GLP-1 and PYY). These findings reveal greater small intestinal metabolic and microbial plasticity during food ingestion than previously thought and suggest an underappreciated route for oral bacteria, including potential pathogens and pathobionts, to reach the ileum via the food bolus and impact metabolism. Our unique dataset allows us to explore the interplay between local and systemic metabolism, microbiota, and host physiology, with implications for metabolic health. ISRCTN registration: ISRCTN18097249.