Swallowable smart capsule for targeted gastrointestinal microbiome sampling

项目摘要/摘要 人类胃肠道(GI)是体内发现的细菌种类最多的地方，通常 被称为肠道微生物区系。这种多样而复杂的微生物群落在功能上扩展了宿主 基因组，严重影响新陈代谢、生理、营养和免疫功能。当前的方法 评估人类肠道微生物区系的基础是粪便采样、可视化和各种内窥镜检查- 辅助活组织检查技术。内窥镜辅助技术是侵入性的，通常无法检索 取自小肠的样本。虽然粪便样本提供了非侵入性评估，但它们无法 通过胃肠道保存细菌的空间和时间信息。因此，我们建议 开发一种基于可食用非侵入性智能采样胶囊(SSC)的设备，将提供有针对性的 活体肠道微生物样本。开发的技术将允许对影响的独特见解 活的微生物和其他微生物区系调节器在肠道微生物区系中很难接触到GI。 在项目的R21阶段，我们将设计和开发两个SSC，在 分别是小肠或大肠。这些SSC由丙烯酸外壳组成，将容纳一个 吸收水凝胶和透气膜，以及检测胶囊的非磁性示踪剂 粪便中的排泄物。这种水凝胶起到被动致动器的作用，在肿胀时，它会吸入 肠液及其含有的微生物群，并密封胶囊。单层pH触发和双pH- 微生物引发的聚合物涂层将被用来推迟采样，直到胶囊到达 分别为近端小肠或大肠。在此阶段，深入了解胶囊性能(例如采样 将在体外和饮食控制的猪身上评估这两种SSCs的有效性和可检索性。R33相，有两个 AIMS将在临床上评估低膳食纤维与高膳食纤维的美式健康饮食模式的效果 使用两种已开发的SSCs对人类胃肠道微生物区段的内容。我们将首先努力使 SSC方法学从动物模型到人类受试者。这项原则证明研究将用于 验证从远离测试设施的参与者那里恢复SSC的有效性。我们还将评估 使用FDA在沿胃肠道的适当位置的SSC的目标采样性能- 批准的大肠特异性给药(巴柳氮特)作为试验对照化合物。对于临床来说 研究中，我们将使用两种SSC来评估和比较高纤维和低纤维美式健康的效果 40名青年、中年和老年人群近端小肠和大肠肠道微生物区系的摄食模式 上了年纪的人。这个R21/R33项目的总体目标是生产高度可靠、实用和成本效益高的 智能采样胶囊，适用于专注于胃肠功能和临床的研究和应用 人类健康。完成这项研究将开辟微生物组研究的新领域，使人们能够 以前很难接触到的肠道区域，符合NIH的利益，包括精确营养。

PROJECT SUMMARY/ABSTRACT The human gastrointestinal (GI) tract hosts the largest number of bacterial species found in the body, often referred to as the gut microbiota. This diverse and complex microbial community functionally expands the host genome, critically impacting metabolism, physiology, nutrition, and immune function. Current methods for assessing the human gut microbiota are based on fecal sampling, visualization, and various endoscopy- assisted biopsy techniques. Endoscopy-assisted techniques are invasive and usually incapable of retrieving samples from the small intestine. While stool samples provide noninvasive assessment, they are incapable of preserving spatial and temporal information of the bacteria through the GI tract. Therefore, we propose to develop an ingestible non-invasive smart sampling capsule (SSC)-based device that will provide a targeted sampling of viable gut microbes. The developed technology would allow unique insights into the impact that live microbes and other microbiota modulators have on the gut microbiota in hard-to-access GI regions. In the R21 phase of the project, we will design and develop two SSCs that provide targeted sampling in the small or large intestines, respectively. These SSCs are composed of acrylic casing that will house an absorbent hydrogel and a gas permeable membrane, as well as a nonmagnetic tracer to detect the capsule’s excretion in the feces. The hydrogel acts as a passive actuator such that upon swelling, it aspirates the intestinal fluid with its containing microbiota and seals the capsule. Single-layer pH-triggered and double pH- and microbial-triggered polymeric coatings will be utilized to delay the sampling until the capsule reaches the proximal small or large intestine, respectively. During this phase, in-depth capsule performance (e.g. sampling and retrievability) of the two SSCs will be assessed in vitro and in diet-controlled pigs. The R33 phase with two aims will clinically assess the effects of a U.S.-style Healthy Eating Pattern with low- versus high-dietary fiber content on segmental GI microbiota in humans using the two developed SSCs. We will first work to adapt the SSC methodology from the animal model to human subjects. This proof-of-principle study will be conducted to validate the effectiveness of SSC recovery from participants away from the testing facility. We will also assess the targeted sampling performance of the SSCs at appropriate locations along the GI tract using an FDA- approved large intestine-specific delivery drug (Balsalazide) as a testing control compound. For the clinical study, we will use the two SSCs to assess and compare the effects of high- versus low-fiber U.S.-style Healthy Eating Pattern on the gut microbiota in the proximal small and large intestine of 40 young, middle-aged, and older adults. The overall goal of this R21/R33 project is to produce highly reliable, practical, and cost-effective smart sampling capsules, suitable for use for research and clinical applications focused on GI function and human health. Accomplishing this research will open new areas of microbiome research, enabling access to previously hard-to-access regions of the gut, consistent with NIH interests, including precision nutrition.