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.

A.T and T.S, as employee and CEO/co-founders of Pelican Health respectively, which markets intestinal sampling capsules, may face a conflict of interest due to their roles within the company. D.M, J.P.A and P.C are co-founder of Pelican Health. A.L.G is a co-founder for ALPIONER Therapeutics. P.C.D is an advisor and holds equity in Cybele, BileOmix and Sirenas and a Scientific co-founder, advisor and holds equity to Ometa, Enveda, and Arome with prior approval by UC-San Diego. P.C.D also consulted for DSM animal health in 2023. S.C.P, M.L and G.R are employees of Danone (France and Netherlands). All the other authors, declare that they have no conflict of interest.

NCT05477069

The study is supported by (1) the Direction de la Recherche Clinique et de l Innovation (DRCI), CHUGA, Grenoble, France; (2) Association Nationale Recherche Technologie (ANRT) with a CIFRE fellowship number 2021/0931, Paris, France; and (3) Pelican Health, Grenoble, France. (4) BPIFrance: i-Lab DOS0172081/00. We also acknowledge funding from NIDDK 1R01DK136117-01 granted to P.C.D.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This research was approved by the Grenoble Alpes University Hospital institutional review board and authorized after its filing with the CNIL (Commission nationale de l'informatique et des libertes) according to the French procedure for a monocentric study and has been granted ethical approval by the Personal Protection Committee (CPP) (23 February 2022 and 9 March 2023) and, by the French National Agency for the Safety of Medicines and Health Products (ANSM) (2 June 2022 and 20 March 2023), and it has formally been registered as a study (NCT05477069).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Raw data for dataset are not publicly available to preserve individuals privacy under the European General Data Protection Regulation. Data supporting the findings of this study are available from the author A.L.G and T.S upon request.