Swallowable smart capsule for targeted gastrointestinal microbiome sampling

用于靶向胃肠道微生物组采样的可吞咽式智能胶囊

• 批准号: 10425078
• 负责人: WAYNE W CAMPBELL
• 金额: $ 18.52万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-13 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10425078
• 关键词: 16S ribosomal RNA sequencing; Address; Adult; Age; Anaerobic Bacteria; Animal Model; Animals; Area; Aspirate substance; Bacteria; Biopsy; Butyrates; Cell Membrane Permeability; Clinical; Clinical Research; Clinical Trials; Collection; Complex; Consumption; Controlled Clinical Trials; Deglutition; Development; Devices; Diet; Dietary Fiber; Double-Blind Method; Drug Delivery Systems; Elderly; Endoscopy; Environment; Excretory function; FDA approved; Family suidae; Feces; Female; Fiber; Gases; Gastroenterology; Gastrointestinal Contents; Gastrointestinal tract structure; Genome; Goals; Health; Healthy Eating; Human; Hydrogels; In Vitro; Ingestion; Interdisciplinary Study; Intestines; Large Intestine; Liquid substance; Location; Measures; Metabolism; Methodology; Methods; Microbe; Participant; Pattern; Performance; Phase; Physiology; Polymers; Positioning Attribute; Preclinical Testing; Randomized; Recovery; Reproducibility; Research; Research Personnel; Retrieval; Safety; Sampling; Site; Small Intestines; Specificity; Swelling; Techniques; Technology; Testing; Time; Tracer; United States National Institutes of Health; Validation; Visualization; Volatile Fatty Acids; Work; age group; base; biomaterial compatibility; capsule; clinical application; cost; cost effective; design; detector; effectiveness validation; experience; feeding; gastrointestinal; gastrointestinal function; gut microbes; gut microbiome; gut microbiota; high reward; high risk; host microbiome; host microbiota; host-microbe interactions; human microbiota; human subject; immune function; in vitro Model; in vivo; indexing; innovation; insight; interest; male; microbial; microbial community; microbiome; microbiome research; microbiota; middle age; nutrition; porcine model; precision nutrition; preclinical study; preservation; seal; stool sample

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.

项目摘要/摘要 人类胃肠道（GI）占体内发现的细菌数量最多，通常 称为肠道菌群。这种多样而复杂的微生物社区在功能上扩展了主机 基因组，严重影响代谢，生理，营养和免疫功能。当前方法 评估人肠道菌群是基于粪便采样，可视化和各种内窥镜检查 辅助活检技术。内窥镜辅助技术是侵入性的，通常无法检索 小肠的样品。虽然粪便样品提供无创评估，但它们却无能为力 通过胃肠道保留细菌的空间和临时信息。因此，我们建议 开发一种可易感的非侵入性智能采样胶囊（SSC）的设备，该设备将提供目标 可行肠道微生物的采样。开发的技术将使对影响的独特见解 活的微生物和其他微生物群调节剂具有难以访问的GI区域的肠道微生物群。 在项目的R21阶段，我们将设计和开发两个SSC，可在 小肠或大肠。这些SSC由丙烯酸外壳组成，可以容纳 吸收性水凝胶和气体可渗透膜以及非磁示踪剂可检测胶囊的 粪便中排泄。水凝胶充当一个被动执行器，使得肿胀后，它使得 肠液中含有菌群并密封胶囊。单层pH触发和双pH- 和微生物触发的聚合物涂层将用于延迟采样，直到胶囊到达 小肠近端或大肠。在此阶段，深入的胶囊性能（例如采样 两种SSC的可检索性将在体外和饮食控制的猪中进行评估。 R33阶段有两个 AIMS将在临床上评估使用低纤维纤维的美国风格健康饮食模式的影响 使用两个已发达的SSC的人类中分段胃肠道微生物群的内容。我们将首先努力适应 从动物模型到人类受试者的SSC方法论。此原则研究将进行 验证参与者从测试设施中恢复的有效性。我们还将评估 使用FDA-在适当位置在适当位置的SSC的靶向采样性能使用FDA- 批准的大肠特异性递送药物（巴拉唑）是一种测试控制化合物。用于临床 研究，我们将使用这两种SSC评估和比较高纤维低纤维美国风格的影响 在40岁，中年和 老年人。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 智能采样胶囊，适用于研究和临床应用，重点是胃肠道功能和 人类健康。完成这项研究将开放微生物组研究的新领域，从而可以访问 以前肠道的难以访问区域，与NIH的利益一致，包括精密营养。