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

对消化疾病的预防和治疗反应是通过详细了解如何维持健康状态来了解的，因此努力了解肠道微生物如何促进正常的肠道发育对肠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(每个人200美元)，这严重限制了寻找肠道细菌与健康或患病宿主之间的致病联系的研究，只能由几个资金充足的研究小组进行。这项拟议的工作建立了美国蟑螂(PeriPlaneta Americana)作为低成本(每个人1美元)的无菌模式系统，用于对肠道界面上的微生物群落-宿主相互作用进行假设驱动的调查。无菌美洲大黄菌是一个有用的补充实验平台，因为它有许多与哺乳动物相同的肠道细菌，其中许多是可培养的，并表现出许多与无菌啮齿动物相同的消化和发育异常。这项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肠道地方性细菌，以识别能够引起正常发育和生长的物种。未来的工作将利用美洲锥虫与生俱来的杂食性来研究人类饮食如何影响肠道细菌动态以及随后宿主胃的健康和发育。此外，霍华德大学的优秀本科生将与俄亥俄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将在历史上为黑人大学和拉美裔服务机构的贡献演讲，以积极促进学术研究事业，并为俄亥俄州立大学的暑期研究机会项目招募高素质的本科生。肠道上皮是少数几个宿主、微生物和环境融合并产生重大进化和生态后果的地点之一。对消化疾病的预防和治疗反应是通过详细了解正常或健康状态是如何出现和维持的，因此努力了解肠道微生物如何促进正常的肠道发育也是非常有意义的。细菌物种对肠道健康的贡献可能是具有挑战性的，因为肠道群落由许多具有重叠功能的物种组成。无菌啮齿动物模型经常被使用，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)，这限制了寻找肠道细菌与健康或患病宿主之间致病联系的研究。拟议的工作旨在建立美国蟑螂(美洲大蠊)的效用，作为详细描述肠道界面微生物群落-宿主相互作用的实验平台，并提供低成本(每只蟑螂1美元)的替代工具，用于假设检验和可靠的初步数据收集。无菌美洲对虾(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并使用这一新的实验性微生物组研究工具包的基础上，以1)鉴定对肠道结构和消化发育至关重要的肠道共生菌，以及2)检测在肠道共生菌存在的情况下在肠道组织中差异表达的宿主基因产物。

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.