NSF PRFB FY22: Gut instinct: environmental and reproductive influences on microbiome contributions to neuroinflammation

该行动资助了2022财年的NSF生物学博士后研究奖学金，即调查基因组，环境和表型之间相互作用的生命规则的综合研究。该研究金支持研究员的研究和培训，以创新的方式为生活规则领域做出贡献。肠道是数万亿细菌的家园。这些微生物，统称为微生物组，与宿主的身体一起工作。先前的研究表明，根据宿主的生理学，肠道微生物组的功能可以通过外部线索改变，这些变化会导致宿主体内的后果。该项目以斑胸草雀为模型，探索压力（一种环境变量）和卵巢和睾丸（一种内部变量）的激素如何改变微生物组，从而改变宿主的大脑炎症。尽管肠道微生物组对行为和健康产生了深远的影响，但了解微生物组如何影响大脑的许多复杂性仍未得到探索。这个项目将提供更多的知识，了解各种环境和内部条件如何改变这种共生关系，从而影响大脑。研究员还将开发和评估改进的协议，以增加本科生和高中生的实验室可访问性。 该项目的第一个目标是确定环境压力是否会改变男性与女性的微生物组，从而改变神经炎症。雄性和雌性雀，有或没有微生物组的存在将被放置在社会隔离或群体住房。将分别通过聚合酶链反应（PCR）和碳水化合物利用分析评估微生物组组成和功能。然后对所有动物进行穿透性脑损伤，并通过定量PCR和免疫反应性分析促炎和抗炎途径评估其神经免疫应答。第二个目的是检查性腺激素对微生物群组成和功能以及随后的神经炎症对穿透性脑损伤的反应的贡献。如前所述，在评估微生物组和神经炎症特征之前，将用药理学药物治疗动物以改变雄激素或雌激素水平。除了这项研究之外，该研究员还将努力培养在主要本科院校任教和开发适合本科院校的研究项目所需的技能。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响力审查标准进行评估，被认为值得支持。

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2022, Integrative Research Investigating the Rules of Life Governing Interactions Between Genomes, Environment and Phenotypes. The fellowship supports research and training of the fellow that will contribute to the area of Rules of Life in innovative ways. The gut is home to trillions of bacteria. These microorganisms, collectively known as the microbiome, work together with their host’s body. Prior research has shown that, depending on host physiology, gut microbiome function can be altered by outside cues, with these changes leading to consequences in the host body. Using zebra finch birds as a model, this project explores how stress (an environmental variable) and hormones from the ovaries and testes (an internal variable) change the microbiome and thus alter host brain inflammation. Despite far-reaching consequences of the gut microbiome to behavior and health, many complexities of understanding how the microbiome affects the brain remain unprobed. This project will provide additional knowledge of how various environmental and internal conditions can alter this symbiosis to affect the brain. The Fellow will also development and assess improved protocols to increase lab accessibility for undergraduates and high school students. The first aim of this project will determine whether environmental stress alters the microbiome differently in males vs. females to alter neuroinflammation. Male and female finches, with or without microbiome presence will be placed in social isolation or group housing. Microbiome composition and function will be assessed via polymerase chain reaction (PCR) and carbohydrate utilization analysis, respectively. All animals will then be subjected to penetrating brain injury and their neuroimmune responses assessed via analysis of pro- and anti-inflammatory pathways by quantitative PCR and immunoreactivity. The second aim examines the contributions of gonadal hormones to microbiome composition and function and subsequent neuroinflammation in response to penetrating brain injury. Animals will be treated with pharmacological agents to alter androgen or estrogen levels before assessing the microbiome and neuroinflammation profiles as previously stated. In addition to this research, the Fellow will also be working towards developing the skills necessary to teach at and develop a research program suitable for a primarily undergraduate institution.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.