CLINICAL SAMPLING OF SMALL INTESTINE LUMINAL CONTENT FOR MICROBIOME MULTI-OMICS ANALYSIS: A PERFORMANCE ANALYSIS OF THE SMALL INTESTINE MICROBIOME ASPIRATION (SIMBA) CAPSULE AND BENCHMARKING AGAINST ENDOSCOPY
Authors: Wang Gang , Bundalovic-Torma Cedoljub , Menon Sharanya , Bruehlmann Sabina , Wilsack Lynn , Rehak Renata , Bagheri Sahar , Banoei Mohammad M. , Lou Lawrence , Nasser Yasmin , Woo Matthew , Lewis Ian , McCoy Kathy D. , Andrews Christopher N. 
Published: April 2024

ABSTRACTObjectiveThe small intestine (SI) microbiome is increasingly implicated in both functional gastrointestinal (GI) disorders and a wide range of systemic diseases. However, owing to limitations of traditional GI sampling approaches, the SI remains challenging to directly access on a large scale. This work presents the Small Intestinal MicroBiome Aspiration Capsule (SIMBA) as an effective means for sampling SI luminal content.DesignIn an observational clinical study, SIMBA capsules were ingested by both healthy individuals and Irritable Bowel Syndrome (IBS) patients on two successive visits. On a first visit, X-ray scans were used to evaluate SI targeting accuracy. On a second visit, SIMBA capsule ingestion was paired with duodenal endoscopy and saliva samples for reference. For both visits, SIMBA capsules were retrieved with matching fecal samples to evaluate effective sealing during GI transit.ResultsX-ray monitoring confirmed all capsules sampled from the distal small intestine with a few (5 of 49) sealing in the proximal colon. Overall, 94% of capsules were retrieved by subjects with median total gut transit time of 47 hours (IQR 24-54). Capsule sampling location and duration was also not significantly affected by IBS. Multi-omics analysis showed that microbiota and metabolomic composition of SIMBA capsules were significantly different to fecal samples, and similar to endoscopic aspirate and cytological brush sampling.ConclusionsThe SIMBA capsule reliably captures and preserves SI luminal fluid in a clinically relevant context that is suitable for multi-omics data analysis, comparable to duodenal aspirate, and complements fecal sampling in its broad applicability of use.KEY MESSAGESWhat is already known on this topicResearch into the gastrointestinal (GI) microbiome and its role in health and disease is almost completely biased towards the colon due to the reliance on fecal sampling.Owing to the lack of reliable and scalable sampling approaches, our knowledge of the small intestine (SI) microbiome is significantly lagging by comparison.What this study addsThis study presents the Small Intestine Microbiome Aspiration (SIMBA) capsule which targets the distal SI in a reliable and reproducible fashion and collects high-quality multi-omics datasets that are on par with “gold-standard” endoscopic sampling.The SIMBA capsule was compared against established sampling methodologies, providing a multi-omics glimpse into the entire biogeographic diversity of the GI tract, revealing substantial and biologically meaningful differences in both microbiome and metabolic profiles that reinforce the significant difference between SI and feces.Overall, the SIMBA capsule demonstrates clear and reproducible differences in microbiome composition of the SI that is otherwise lacking from traditionally used fecal sampling.How this study might affect research, practice or policyThe SIMBA capsule collects high-quality multi-omics datasets that will enable significant insights into the SI microbiome function in health and disease and is ideal for use in research, large-scale clinical or population studies, and diagnostic applications.