Spatiotemporal Profiling of The Human Small Intestine Metabolome and Microbiome
The gastrointestinal tract is a dynamic system where different anatomical regions interact to regulate whole-body physiology. Diet-derived and microbially linked metabolites contribute significantly to inter-individual variation, but spatially and temporally resolved data on human dietary metabolism across the small intestine remain limited. Here, we use naso-enteral intubation to collect longitudinal samples from the stomach, duodenum, and ileum of 10 healthy participants consuming structurally varied legume-based meals. Gastric and duodenal samples were collected up to 3 hours postprandially and ileal samples up to 8 hours. Metabolite profiling was performed using NMR spectroscopy, and shotgun metagenomic sequencing enabled microbial strain tracking from the oral cavity to the ileum. We find that metabolite profiles and microbial communities exhibit rapid spatial and temporal dynamics, with oral bacterial strains detected in the ileum. The structural properties of food influence metabolite composition and microbial populations, correlating with gut hormone responses (GLP-1 and PYY). These findings reveal greater small intestinal metabolic and microbial plasticity during food ingestion than previously appreciated and suggest a route for oral bacteria, including potential pathogens and pathobionts, to reach the ileum via the food bolus. This study highlights the interplay between diet, microbiota, and host physiology, with implications for metabolic health.
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