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: 10642943
• 负责人: WAYNE W CAMPBELL
• 金额: $ 22.2万
• 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/10642943
• 关键词: 16S ribosomal RNA sequencing; Address; Adult; Age; Anaerobic Bacteria; Animal Model; Animals; Area; Bacteria; Biopsy; Butyrates; Cell Membrane Permeability; Clinical; Clinical Research; Clinical Trials; Clinical assessments; Collection; Complex; Consumption; Controlled Clinical Trials; 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; Intestinal Absorption; 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; aspirate; 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; manufacture; 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.

项目概要/摘要 人类胃肠道 (GI) 拥有体内发现的最多数量的细菌种类，通常 这种多样化且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、生理学、营养和免疫功能的当前方法。 评估人类肠道微生物群是基于粪便取样、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。 虽然粪便样本可以提供无创评估，但它们无法进行评估。 因此，我们建议通过胃肠道保存细菌的空间和时间信息。 开发一种基于可摄入非侵入性智能采样胶囊（SSC）的设备，该设备将提供有针对性的 所开发的技术可以对存活的肠道微生物进行采样，从而对影响产生独特的见解。 活微生物和其他微生物群调节剂对难以进入的胃肠道区域的肠道微生物群有影响。 在该项目的R21阶段，我们将设计和开发两个SSC，在 这些 SSC 分别由丙烯酸外壳组成，可容纳一个小肠或大肠。 吸收性水凝胶和透气膜，以及用于检测胶囊的非磁性示踪剂 水凝胶作为被动致动器，在膨胀时吸入粪便。 肠液及其含有的微生物群并密封胶囊。 微生物触发的聚合物涂层将用于延迟采样，直到胶囊到达 分别近端小肠或大肠 在此阶段，深入胶囊性能（例如采样）。 将在体外和饮食控制的猪中评估两种 SSC 的 R33 阶段。 目标将临床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 我们将首先努力适应使用两个开发的 SSC 的人类分段胃肠道微生物群的内容。 这项原理验证研究将用于从动物模型到人类受试者的 SSC 方法。 我们还将评估远离测试设施的参与者的 SSC 恢复效果。 使用FDA-在胃肠道适当位置进行SSC的目标采样性能 批准大肠特异性递送药物（巴柳氮）作为临床测试对照化合物。 研究中，我们将使用两个 SSC 来评估和比较高纤维与低纤维美式健康饮食的效果 饮食模式对 40 名青年、中年人和大肠近端小肠和大肠肠道菌群的影响 R21/R33 项目的总体目标是生产高度可靠、实用且具有成本效益的产品。 智能采样胶囊，适用于关注胃肠道功能和 完成这项研究将开辟微生物组研究的新领域，使人们能够接触到人类健康。 以前难以进入的肠道区域，符合 NIH 的兴趣，包括精准营养。

项目成果

Biocompatibility and Safety Assessment of Combined Topical Ozone and Antibiotics for Treatment of Infected Wounds.

局部臭氧和抗生素联合治疗感染伤口的生物相容性和安全性评估。

• DOI: 10.1021/acsbiomaterials.2c01548
• 发表时间: 2023
• 期刊: ACS biomaterials science & engineering
• 影响因子: 5.8
• 作者: Roth,Alexander;Krishnakumar,Akshay;McCain,RobynR;Maruthamuthu,MuraliKanaan;McIntosh,MacKenzie;Chen,YueXiang;Cox,AbigailD;HopfJannasch,AmberS;Nguyen,Juliane;Seleem,MohamedN;Rahimi,Rahim
• 通讯作者: Rahimi,Rahim

Smart capsule for monitoring inflammation profile throughout the gastrointestinal tract.

用于监测整个胃肠道炎症状况的智能胶囊。

• DOI: 10.1016/j.biosx.2023.100380
• 发表时间: 2023
• 期刊: Biosensors & bioelectronics: X
• 作者: Gopalakrishnan,Sarath;Thomas,Rithu;Sedaghat,Sotoudeh;Krishnakumar,Akshay;Khan,Sadid;Meyer,Trevor;Ajieren,Hans;Nejati,Sina;Wang,Jiangshan;Verma,MohitS;Irazoqui,Pedro;Rahimi,Rahim
• 通讯作者: Rahimi,Rahim

Non-destructive processing of silver containing glass ceramic antibacterial coating on polymeric surgical mesh surfaces.

聚合物手术网表面含银玻璃陶瓷抗菌涂层的无损处理。

• DOI: 10.1039/d3nr01317k
• 发表时间: 2023
• 期刊: Nanoscale
• 影响因子: 6.7
• 作者: Zareei,Amin;Kasi,Venkat;Thornton,Allison;Rivera,UlissesHeredia;Sawale,Manoj;Maruthamuthu,MuraliKannan;He,Zihao;Nguyen,Juliane;Wang,Haiyan;Mishra,DharmendraK;Rahimi,Rahim
• 通讯作者: Rahimi,Rahim

Smart capsule for targeted proximal colon microbiome sampling.

• DOI: 10.1016/j.actbio.2022.09.050
• 发表时间: 2022-12
• 期刊: Acta biomaterialia
• 影响因子: 9.7
• 作者: Nejati S;Wang J;Sedaghat S;Balog NK;Long AM;Rivera UH;Kasi V;Park K;Johnson JS;Verma MS;Rahimi R
• 通讯作者: Rahimi R