权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Micro-engineered capsules for spatial sampling of microbiome in vivo

用于体内微生物组空间采样的微工程胶囊

基本信息

批准号：
10269448
负责人：
Sameer R Sonkusale
金额：
$ 15.99万
依托单位：
TUFTS UNIVERSITY MEDFORD
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10269448
关键词：
3D Print Address Administrative Supplement Animal Model Animals Antibiotics Ascending colon Autopsy Award Budgets Cells Cellulose Charge Chronic Disease Color Complementary DNA Complex Custom DNA Data Diet Dietary Fiber Dietary Intervention Ecosystem Engineering Enterocytes Epithelial Cells Escherichia coli Exploratory/Developmental Grant for Diagnostic Cancer Imaging Family suidae Feces Funding Gastrointestinal tract structure Gene Expression Generations Genes Genetic Transcription Goals Health High-Throughput Nucleotide Sequencing Human In Situ Inflammatory Intestines Inulin Knowledge Laboratories Link Location Metagenomics Methods Modeling Motor Organ Parents Pectins Physiological Population Postdoctoral Fellow Pump RNA Research Research Personnel Research Proposals Risk Rodent Running Sampling Structure Suspensions Technology Testing Training Weaning body system capsule colon microbiota cost design dietary dietary control dietary supplements dysbiosis experimental study feasibility testing graduate student gut microbiome gut microbiota ileum improved in vitro testing in vivo insoluble fiber intestinal epithelium jejunum magnetic field microbial microbiome microbiota motor control novel pandemic disease parent project prebiotics prototype rRNA Genes response soluble fiber transcriptome transcriptome sequencing

项目摘要

ABSTRACT OF SUPPLEMENTAL RESEARCH This proposal is submitted in response to PA-20-227 (Administrative Supplements for Research on Dietary Supplements). The Specific Aims of parent award R21 AI144521 are (1) to design, fabricate and test micro- engineered ingestible capsules for sampling the gastro-intestinal tract; (2) to test the capsules in pigs. The parent project seeks to demonstrate the feasibility of non-invasively sampling the gastro-intestinal tract in a realistic animal model and to validate the ingestible capsule technology. Non-invasive sampling of the gastro-intestinal tract will advance the study of the intestinal microbiome and its beneficial functions. We are seeking supplemental funding to leverage research conducted under the parent award to study the effect of dietary supplements on the bacterial microbiota populating the gastro-intestinal tract. Although the intestinal microbiota's response to various perturbations, like diet, antibiotics or inflammatory conditions has been studied, the bulk of this research has been conducted in humans and rodents. For obvious reasons, most of these studies rely on the analysis of fecal DNA and fecal metabolites, which do not closely mirror changes in more proximal sections of the GI tract, like the jejunum, ileum and ascending colon. Supplemental funding would allow us to: 1) increase the number of pigs to study the effect of 3 commonly used prebiotic supplements (inulin, pectin, cellulose) on the microbiota populating different organs of the GI tract, 2) expand the scope of the project beyond the bacterial microbiota to the intestinal epithelium and its transcriptional response to diet. To non-invasively investigate the response of the intestinal epithelium to changes in diet, we are proposing to use RNA-Seq to analyze the "exfoliome", i.e., the transcriptome of exfoliated epithelial cells excreted in feces. To assess the quality of the exfoliome, we will compare exfoliome RNA-Seq data with RNA- Seq data obtained from epithelial cells collected directly from different GI organs after the animal has been sacrificed. The analysis of the pig intestinal exfoliome seeks to evaluate whether changes in enterocyte gene expression are detectable non-invasively by sequencing fecal cDNA. Although supplementary experiments expand the scope of the parent award to include dietary intervention, this research is not dependent on the optimization of the ingestible capsule. Pigs used for testing the capsules will be leveraged to investigate the following Supplemental Specific Aims: 1) to assess the impact of inulin, pectin and cellulose on the bacterial microbiota sampled in vivo using an ingestible capsule and collected post-mortem from different GI organs; 2) to apply RNA-Seq to evaluate the feasibility of characterizing the transcriptome of exfoliated enterocytes from pigs fed control and test diet. Thus, supplemental experiments will use a well-defined dietary intervention to expand the scope of the parent award in two directions; 1) to assess the effect of diet on commensal bacterial which are not present in fecal DNA; 2) to test the feasibility of non- invasively characterizing the enterocyte transcriptome and its response to dietary perturbation.

补充研究摘要本提案是根据PA-20-227(膳食研究行政补充资料)提交的补充剂)。家长奖R21 AI144521的具体目标是：(1)设计、制造和测试微处理器设计了用于胃肠道采样的可食用胶囊；(2)在猪身上进行试验。母公司的项目旨在证明非侵入性胃肠道采样的可行性。建立了逼真的动物模型，并验证了可食胶囊技术。非侵入性采样胃肠道将促进对肠道微生物及其有益功能的研究。我们是寻求补充资金，以利用在家长奖下进行的研究，以研究膳食补充剂对胃肠道细菌微生物区系的影响。虽然肠道微生物区系对各种扰动的反应，如饮食、抗生素或炎症条件在研究中，这项研究的大部分是在人类和啮齿动物身上进行的。出于显而易见的原因，大多数这些研究依赖于对粪便DNA和粪便代谢物的分析，这些分析并不能很好地反映胃肠道更近端的部分，如空肠、回肠和升结肠。补充资金可以让我们：1)增加猪的数量来研究3种常用的益生素的效果补充剂(菊粉、果胶、纤维素)对胃肠道不同器官中微生物区系的影响，2)扩大该项目的范围从细菌微生物区系到肠道上皮细胞及其转录对饮食的反应。为了非侵入性地研究肠道上皮对饮食变化的反应，我们正在提议使用RNA-Seq来分析“剥离体”，即脱落的上皮细胞的转录组从粪便中排出。为了评估剥离体的质量，我们将剥离体RNA-Seq数据与RNA-Seq数据进行比较。直接从不同的胃肠道器官采集的上皮细胞的SEQ数据牺牲了。对猪肠道脱落细胞的分析试图评估肠细胞基因的变化通过对粪便DNA测序，可以非侵入性地检测到表达。虽然补充实验扩大家长奖励的范围，包括饮食干预，这项研究不依赖于口服胶囊剂的优化。用来测试胶囊的猪将被用来调查以下补充具体目标：1)评估菊粉、果胶和纤维素对使用可食用胶囊在体内采集细菌微生物区系，并在死后从 2)应用RNA-Seq技术鉴定转录组的可行性饲喂对照日粮和试验日粮的猪的脱落肠细胞。因此，补充实验将使用明确的饮食干预措施，从两个方向扩大家长奖励的范围；1)评估饮食对粪便DNA中不存在的共生菌的影响；2)测试非肠道细胞转录组的侵袭性特征及其对饮食扰动的反应。