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Bacteria-mediated gut development and symbiont genome evolution in a model invertebrate

无脊椎动物模型中细菌介导的肠道发育和共生体基因组进化

基本信息

批准号：
1656786
负责人：
Zakee Sabree
金额：
$ 50.99万
依托单位：
Ohio State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2022-11-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1656786&HistoricalAwards=false
关键词：
Bacteria mediated gut development symbiont

项目摘要

Preventive and therapeutic responses to digestive diseases are well-informed by a detailed understanding of how healthy states are maintained, and thus efforts to understand how gut microbes contribute to normal gut development is of significant interest to gut gastric health. While rodent-based, germ-free animal models are most commonly used, they are expensive ($200/individual) to maintain and use, severely constraining research into finding causative links between gut bacteria and healthy or diseased host states to a few, well-funded research groups. The proposed work establishes the American cockroach (Periplaneta americana) as low-cost ($1/individual) germ-free model system for conducting hypothesis-driven investigations into microbial community-host interactions at the gut interface. Germ-free P. americana is a useful complementary experimental platform because it shares many of the same gut bacteria found in mammals, many of whom are cultivable, and exhibits many of the same digestive and developmental abnormalities observed in germ-free rodents. The proposed work will reintroduce endemic gut bacteria via fecal transplants and artificial assemblages of cultivated bacteria to identify species that elicit normal development and growth. Future work will exploit P. americana's inherent omnivory to examine how human diets impact gut bacterial dynamics and subsequent host gastric health and development. Furthermore, high-achieving undergraduates from Howard University will be partnered with Ohio State University postdocs and graduate students to participate in proposed activities as summer research assistants and the PI will give contributed talks at historically black universities and Hispanic serving institutions to actively promote academic research careers and recruit high-achieving undergraduates for the Ohio State University summer research opportunities program.The gut epithelium is among the few sites in which host, microbes and the environment converge with significant evolutionary and ecological consequences. Prevention and therapeutic responses to digestive diseases are well-informed by a detailed understanding of how normal or healthy states emerge and are maintained, and thus efforts to understand how gut microbes contribute to normal gut development is also of significant interest. The contributions of bacterial species to gut health can be challenging because gut communities are comprised of many species with overlapping functional abilities. Germ-free rodent models are often used because they can be inoculated with desired bacteria and then host conditions can be assessed. Unfortunately, germ-free rodents are expensive to maintain and use ($200/individual) and this limits research into finding causative links between gut bacteria and healthy or diseased host states. The proposed work seeks to establish the utility of the American cockroach (Periplaneta americana) as an experimental platform for detailing microbial community-host interactions at the gut interface and to provide low-cost ($1/roach), alternative tools for hypothesis-testing and robust preliminary data collection. Germ-free P. americana (GF-PA) can be reared without antibiotics and substantial preliminary data indicates that many of the gut structural and cellular abnormalities associated with germ-free rodents are observed. The proposed work will build on and use this new experimental microbiome research tool kit to 1) identify gut symbionts critical for gut structural and digestive development and 2) detect host gene products differentially expressed in gut tissues in the presence of gut symbionts.

对消化系统疾病的预防和治疗反应是通过详细了解如何保持健康状态而获得的，因此了解肠道微生物如何促进正常肠道发育的努力对肠道胃健康具有重要意义。虽然基于啮齿动物的无菌动物模型是最常用的，但它们的维护和使用成本很高（200美元/人），严重限制了研究肠道细菌与健康或患病宿主状态之间的因果关系。拟议的工作建立了美国蟑螂（美洲大蠊）作为低成本（1美元/个体）的无菌模型系统进行假设驱动的调查肠道界面的微生物群落-宿主相互作用。无菌美洲原杆菌是一个有用的补充实验平台，因为它与哺乳动物中发现的许多相同的肠道细菌相同，其中许多是可培养的，并且表现出许多与无菌啮齿动物中观察到的相同的消化和发育异常。拟议的工作将通过粪便移植和人工培养细菌的组合重新引入地方性肠道细菌，以确定引起正常发育和生长的物种。未来的工作将利用美洲原住民固有的杂食性来研究人类饮食如何影响肠道细菌动力学以及随后的宿主胃健康和发育。此外，委员会认为，来自霍华德大学的优秀本科生将与俄亥俄州州立大学的博士后和研究生合作，作为暑期研究助理参加拟议的活动，PI将在历史悠久的黑人大学和西班牙裔服务机构进行演讲，以积极促进学术研究事业，并招募高水平的获得俄亥俄州州立大学暑期研究机会计划的本科生。肠道上皮是宿主，微生物和环境的融合带来了重大的进化和生态后果。对消化系统疾病的预防和治疗反应通过详细了解正常或健康状态如何出现和维持而得到充分了解，因此了解肠道微生物如何促进正常肠道发育的努力也具有重大意义。细菌物种对肠道健康的贡献可能具有挑战性，因为肠道群落由许多具有重叠功能能力的物种组成。经常使用无菌啮齿动物模型，因为它们可以接种所需的细菌，然后可以评估宿主条件。不幸的是，无菌啮齿动物的维护和使用成本很高（200美元/只），这限制了研究肠道细菌与健康或患病宿主状态之间的因果关系。拟议的工作旨在建立美国蟑螂（美洲大蠊）的效用作为一个实验平台，详细说明肠道界面微生物群落-宿主相互作用，并提供低成本（1美元/蟑螂），替代工具的假设测试和强大的初步数据收集。无菌美洲大蠊（GF-PA）可以在没有抗生素的情况下饲养，大量的初步数据表明，观察到许多与无菌啮齿动物相关的肠道结构和细胞异常。拟议的工作将建立在这个新的实验微生物组研究工具包的基础上，并使用它来1）识别对肠道结构和消化发育至关重要的肠道共生体，2）检测肠道共生体存在时肠道组织中差异表达的宿主基因产物。