Objective: The 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. Design: In 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. Results: X-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. Conclusions: The 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.

CNA has an equity interest in and is a member of the scientific advisory board for Nimble Science.

NCT04094558

This study was supported by the National Research Council of Canada Industrial Research Assistance Program (NRC IRAP), an Alberta Innovate Accelerating Innovations into CarE (AICE) grant, and partially by a Clinical Problems Incubator Grant from the Snyder Institute for Chronic Disease at the University of Calgary. M.M.B. is supported by a Grant from MITACs as well as a grant from the Natural Sciences and Engineering Research Council of Canada (NSERC; DG04547). I.A.L. is supported by an Alberta Innovates Translational Health Chair. Metabolomics data were acquired at the Calgary Metabolomics Research Facility, which is part of the Alberta Centre for Advanced Diagnostics (ACAD; PrairiesCan RIE #22734) and is supported by the International Microbiome Centre and the Canada Foundation for Innovation (CFI-JELF 34986).

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This study was conducted under the guidance and approval of the University of Calgary Conjoint Ethics Review Board (REB19-0957) and Investigational Testing Authorization from Health Canada (ITA 310032).

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