Profiling the human luminal small intestinal microbiome using a novel ingestible medical device.

The invasive nature of sample collection for studying the small intestinal (SI) microbiome often results in its poor characterization. This study evaluated a novel ingestible medical device (MD) for SI luminal sample collection. A monocentric interventional trial (NCT05477069) was conducted on 15 healthy subjects. Metagenomics, metabolomics and culturomics assessed the MD's effectiveness in characterizing the healthy SI microbiome and identifying potential biomarkers. The SI microbiota differed significantly from the fecal microbiota, displaying high inter-individual variability, lower species richness, and reduced alpha diversity. A combined untargeted and semi-targeted LC-MS/MS metabolomics approach identified a distinct SI metabolic footprint, with bile acids and amino acids being the most abundant classes of metabolites. Host and host/microbe-derived bile acids were particularly abundant in SI samples. The application of a fast culturomics approach to two SI samples enabled species-level characterization, resulting in the identification of 90 bacterial species, including five potential novel species. The present study demonstrates the efficacy of our novel sampling MD in enabling comprehensive SI microbiome analysis through an integrative multi-omics approach, allowing the identification of distinct microbiome signatures between SI and fecal samples.