Spatially and Temporally Precise Microbiome Profiling in the Small Intestine using the SIMBA Capsule with X-ray tracking

Few minimally invasive options for sampling the small intestinal (SI) luminal fluid exist to study the SI microbiota in health and disease. To address the lack of tools and methods to study GI regions that are difficult to access, Nimble Science developed a fully autonomous and passive sampling method, the Small Intestine MicroBiome Aspiration (SIMBATM) capsule, for convenient, high-quality, and reliable sampling to study the diet-microbiota interactions in the SI. The sealing efficacy and microbial DNA preservation capacity of the SIMBA capsules was first validated through in vitro simulation assays. Then, a clinical study was conducted with 20 healthy participants to validate the in vivo use of SIMBA capsules to reliably capture samples for SI microbiome analysis before and after an intervention ([NCT04489329][1]). Briefly, participants ingested the capsules at baseline and 7 days later, with a probiotic capsule containing a blend of L. rhamnosus R0011 and B. longum R0175. Following baseline SIMBA capsule ingestion, multiple low-dosage x-ray scans were performed to track the sampling location. Fecal samples corresponding with the baseline and intervention capsule were analyzed for comparison. The SIMBA capsules’ performance in vitro demonstrated the potential for contamination-free sampling with preservation of the microbial communities. Within the clinical study, the capsules performed safely and reliably for collection of SI content. X-ray tracking confirmed that 97.2% of the capsules completed sample collection in the SI regions before reaching the colon. Importantly, our data showed that the capsules sampled in the right area of the intestines and that baseline SIMBA microbiome profile is significantly different from fecal microbiome profile. SIMBA successfully detected a concurrent probiotic intervention in the small intestine, which was not detectable using stool samples. The high accuracy of sampling location and sealing efficacy of the SIMBA capsules makes them potentially useful research tools in clinical trials for studying diet-microbiota interactions in health and disease, and perhaps eventually for the clinical diagnosis of GI tract conditions affecting the SI such as SIBO. ### Competing Interest Statement G.W., S.M., S.Br., are employed by Nimble Science, the company that developed the SIMBA capsule. G.W, S.Br. and C.N.A. are shareholders and hold stock options of Nimble Science. J.A., O.M., and S. Bi are employed by Lallemand Health Solutions, a company that researches, produces, markets, and sells probiotics to business clients but not to consumers, including R0011 and R0175. T.A.T. is employed by Lallemand Bio-Ingredients. ### Clinical Trial NCT04489329 ### Funding Statement This work was supported by the National Research Council of Canada Industrial Research Assistance Program (NRC IRAP) and Alberta Innovate Accelerating Innovations into CarE (AICE) grant. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of the University of Calgary gave ethical approval for this work 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). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The datasets presented in this article were uploaded on the Sequence Read Archive (SRA) under the accession number BioProject ID: PRJNA1031660. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04489329&atom=%2Fmedrxiv%2Fearly%2F2024%2F04%2F03%2F2024.04.02.24305212.atom