The gut microbiome is a complex ecosystem including microorganisms and their biological components such as metabolites. This microbiome is stratified from the duodenum to the rectum with an increase of the microbial density and changes in the diversity. This ecosystem plays a major role in maintaining host’s health by directly influencing metabolic and immune homeostasis. Many studies showed links between the microbiome and pathologies such as metabolic diseases or inflammatory bowel diseases. However, these works were mainly focused on faecal microbiome that is partially representative of the intestinal microbiome. The small intestinal microbiome (SIM) remains mostly uncharacterised due to the difficulties to collect it (invasive endoscopy). Pelican Health has developed a cutting-edge medical device (MD) sampling non-invasively the small intestinal liquid. To prove the safety and the performances of the MD, a proof-of-concept (POC) clinical investigation, named DIGEST, has been performed at the Grenoble Alpes CHU (NCT05477069). The primary objective of the study was to demonstrate the safety and the performances of the MD for at least 12 out of the 15 healthy volunteers included. Safety was assessed in a binary manner as the absence of the occurrence of adverse events of grade ≥3. Performance was linked to the collected volume and visual state. The secondary objectives are related to the analysis of the MD, site of collection and omics analysis. Three kinds of omics have been performed: metagenomics, culturomics and metabolomics. No adverse event has been detected on the included subjects. The primary objective of the trial was reached. Concerning the performances, it has been evaluated that the average volume collected per module was 72µL. The average time for the excretion of the MD was 40h. It has been calculated that 71% of the collected modules were conform. One of the secondary objectives was to perform omics analysis on the two matrices. We conducted culturomics on two small intestinal samples. We cultured and banked more than 100 different bacterial species. The most represented phyla were Bacillota (60%) and Bacteroidota (20%). Five new bacterial species have been discovered. Non targeted and semi-targeted metabolomics on both matrices revealed metabolome differences depending on the sample origin. Intestinal samples showed less interindividual differences compare to faecal samples. For non-targeted metabolomics, 45 metabolites of interest have been targeted for quantification. The clinical investigation proved that the MD is safe for human being. SIM samples collected by the MD are analysable using a multi-omics approach. Differences between the SIM and faecal microbiome in metabolite and microbial composition have been demonstrate. This POC clinical trial will be followed by other clinical trials to ensure the safety of the MD on a larger cohort of healthy volunteers or patients. The perspectives of this work are numerous. The use of the MD could reveal the functional differences between the two microbiomes. The potential to extend this study to clinical trials involving patients holds promise for identifying specific biomarkers linked to various pathologies. It holds immense potential for clinical applications, from diagnostics to treatment strategies.