Gut Microbiome Effects on Brain and Behavior

生活在宿主肠道中的微生物发挥着与营养、对抗疾病和行为有关的多种功能。在许多情况下，肠道微生物组为其宿主执行必要的功能，因此微生物组的破坏会导致异常。在其他情况下，肠道微生物组有助于个体之间的差异，因此个体之间微生物组的差异驱动生理和行为的差异。然而，目前尚不清楚肠道微生物群的功能是否会在宿主的一生中发生变化。此外，虽然各种研究支持肠道微生物在介导宿主行为中的作用，但它们如何影响宿主行为以及介导这种相互作用的因素在很大程度上是未知的。本项目通过研究肠道微生物群如何影响蜜蜂（Apis mellifera）的行为成熟来解决这些重要问题，这涉及到行为从在蜂巢内照顾幼虫和执行蜂巢内其他任务到在蜂巢外觅食花蜜和花粉的转变。这一成熟过程是与年龄相关的劳动分工的基础，因此了解肠道微生物组在这一过程中的作用有望阐明我们对蜂群功能的理解。这些研究的结果也将为宿主-微生物相互作用、动物行为和共生以及肠-脑交流的动力学提供新的见解。该项目将在行为学、基因组学和微生物学方面为家庭机构中处于不同职业阶段的各种学员提供综合培训，并将为当地K-12学生提供独特的外展和培训活动奠定基础。了解肠道微生物群如何促进肠-脑轴的功能是神经科学研究的一个新兴领域，但支持肠-脑交流的机制仍然知之甚少。为了解决这个问题，该项目将利用蜜蜂及其微生物组中最先进的行为，基因组和遗传工具来确定肠道微生物在蜜蜂行为成熟中的作用。具体而言，本项目将：1)结合几种蜜蜂群体水平操作，微生物组测序和行为跟踪来验证微生物组影响蜜蜂行为成熟的假设；2)用与行为成熟密切相关的微生物进行单微生物接种，然后进行代谢组学和转录组学分析，以确定影响行为成熟的特定微生物因素，并将其与对宿主脑功能和生理的特定影响联系起来；3)利用最新开发的蜜蜂微生物组遗传工具包生产转基因微生物，以功能评估特定微生物因素在行为成熟中的作用。实现这些目标将为肠脑轴提供重要的新机制见解，并将确定微生物组是否以及如何影响个体一生中的行为变化。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Microbes living in their host’s gut perform diverse functions related to nutrition, fighting disease, and behavior. In many cases, the gut microbiome performs necessary functions for its host, such that disruptions in the microbiome result in abnormalities. In other cases, the gut microbiome contributes to variation between individuals, such that differences in microbiomes between individuals drive differences in physiology and behavior. However, it is not known whether gut microbiome function can change over the host’s lifetime. Furthermore, while various studies support the role of gut microbes in mediating host behavior, how they influence host behavior and the factors that mediate this interaction are largely unknown. This project addresses these important questions by studying how the gut microbiome influences behavioral maturation in the honey bee, Apis mellifera, which involves a transition in behavior from caring for larvae inside the hive and performing other in-hive tasks, to foraging for nectar and pollen outside of the hive. This maturation process underlies age-related division of labor, so understanding the role of the gut microbiome in this process promises to illuminate our understanding of honey bee colony function. The results of these studies will also provide novel insights into the dynamics of host-microbe interactions, animal behavior and symbiosis, and gut-brain communication. This project will provide integrative training in behavior, genomics, and microbiology to a diverse set of trainees at various career stages within the home institution, and will serve as the foundation for unique outreach and training activities for local K-12 students. Understanding how the gut microbiome contributes to the functioning of the gut-brain axis is an emerging area of study in neuroscience, but the mechanisms supporting gut-brain communication remain poorly understood. To address this problem, this project will utilize state-of-the-art behavioral, genomic and genetic tools in the honey bee and its microbiome to determine the role that gut microbes play in honey bee behavioral maturation. Specifically, this project will: 1) Use a combination of several honey bee colony-level manipulations, microbiome sequencing, and behavioral tracking to test the hypothesis that the microbiome influences behavioral maturation in the honey bee; 2) Perform single-microbe inoculations with microbes robustly associated with behavioral maturation, followed by metabolomic and transcriptomic analyses, in order to identify specific microbial factors that influence behavioral maturation and associate them with specific effects on host brain functioning and physiology; 3) Use a recently developed honey bee microbiome genetic toolkit to produce genetically modified microbes in order to functionally assess the role of specific microbial factors in behavioral maturation. Achieving these objectives will provide important new mechanistic insights into the gut-brain axis, and will determine whether and how the microbiome contributes to changes in behavior over the lifetime of an individual.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.