Molecular mechanisms underlying microbial modulation of host behavior

微生物调节宿主行为的分子机制

• 批准号: 10701899
• 负责人: Chun Nin Adam Wong
• 金额: $ 37.21万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-09 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10701899
• 关键词: Address; Affect; Behavior; Behavior Control; Behavior Disorders; Behavioral; Behavioral Assay; Behavioral Genetics; Biology; Brain; Cells; Choice Behavior; Communication; Complex; Data; Diet; Disease; Drosophila genus; Drosophila melanogaster; Eating Disorders; Endocrine; Feeding behaviors; Five-Year Plans; Food; Food Preferences; Gene Expression Regulation; Genes; Genetic; Genetic Predisposition to Disease; Genetic Transcription; Genomics; Gnotobiotic; Goals; Habits; Health; Human; Individual; Individual Differences; Individuality; Knowledge; Mammals; Maps; Microbe; Molecular; Molecular Target; Neuropeptides; Obesity; Organ; Outcome; Population; Process; Research; Shapes; Signal Transduction; Symbiosis; System; behavioral outcome; behavioral phenotyping; combat; feeding; fly; food environment; gene interaction; gene regulatory network; host-associated microbial communities; host-microbe interactions; metabolomics; microbial; microbiome; microbiome alteration; preference; programs; tool; trait; transcriptome; transcriptomics

A central question in behavioral biology is how environmental and genetic factors shape behavioral traits, allowing for substantial individuality. Homeostatic behaviors like feeding and food preferences are prime examples of genetic predispositions interacting with the food environment to produce diverse feeding habits. However, these programs are further modified by host-associated microbes, suggesting the overall systems controlling behavioral phenotype is far more complex than first anticipated. The critical questions that remain to be addressed are: to what extent do host-microbe interactions contribute to individual differences in behavior? Specifically, how does gene regulation of behavior operate in the context of host-microbe symbiosis? Implicit in this question is the hypothesis that perturbation of host-microbe symbiosis results in aberrant behavioral outcomes in certain individuals or populations, a topic fundamental to human health yet unsolved. The goal of my research program is to define how behaviors are shaped by host-microbe interactions. My lab studies foraging and food choice behaviors in the fly Drosophila melanogaster, using a gnotobiotic system I developed that permits precise configuration of the fly microbiome. I hypothesize that feeding behavior and food preferences are the product of host genetics-microbiome interactions, which determine, in part, an individual’s long-term health. Our recent data show that foraging and diet selection preferences vary by the microbiome, and altering the microbiome triggers transcriptional changes in specific cell clusters within the fly brain, involving genes predicted to affect behavior. In this five-year plan, I will leverage fly genetics and state- of-the-art genomics and metabolomics tools to identify the gene regulatory networks and mechanisms underlying microbial modulation of host behavior. Expected outcomes include comprehensive gut endocrine signaling and inter-organ communication maps at single-cell transcriptome scale and metabolite-gene interactions networks. The causal effects of microbiome-responsive genes, neuropeptides, and metabolites on host feeding behavior and food preferences will be revealed. Since we know little about how the interplay of host genetics and microbiome contribute to complex behavior, my research has the potential to advance fundamental knowledge in behavioral genetics but also to identify genes or processes that may function similarly in Drosophila and mammals as targets to treat behavioral disorders, such as eating disorders and obesity.

行为生物学的一个中心问题是环境和遗传因素如何塑造行为特征， 允许显着的个性。进食和食物偏好等稳态行为是首要因素 遗传倾向与食物环境相互作用产生不同饮食习惯的例子。 然而，这些程序被宿主相关微生物进一步修改，表明整个系统 控制行为表型比最初预期的要复杂得多。仍然存在的关键问题 需要解决的是：宿主-微生物相互作用在多大程度上导致个体行为差异？ 具体来说，行为的基因调控如何在宿主-微生物共生的背景下发挥作用？隐含于 这个问题是这样的假设：宿主-微生物共生的扰动会导致异常的行为 某些个人或人群的结果，这是一个对人类健康至关重要的话题，但尚未解决。 我的研究计划的目标是定义宿主-微生物相互作用如何塑造行为。 我的实验室使用知生系统研究黑腹果蝇的觅食和食物选择行为 我开发了一种可以精确配置果蝇微生物组的技术。我假设喂养行为和 食物偏好是宿主遗传学-微生物组相互作用的产物，这在一定程度上决定了 个人的长期健康。我们最近的数据显示，觅食和饮食选择偏好因物种而异 微生物组，改变微生物组会触发果蝇内特定细胞簇的转录变化 大脑，涉及预计会影响行为的基因。在这个五年计划中，我将利用果蝇遗传学和状态- 最先进的基因组学和代谢组学工具，用于识别基因调控网络和机制 宿主行为的潜在微生物调节。预期结果包括全面的肠道内分泌 单细胞转录组规模和代谢物基因的信号传导和器官间通讯图谱 互动网络。微生物组反应基因、神经肽和代谢物对 宿主的进食行为和食物偏好将被揭示。由于我们对如何相互作用知之甚少 宿主遗传学和微生物组导致复杂的行为，我的研究有潜力推进 行为遗传学的基础知识，还可以识别可能起作用的基因或过程 类似地，在果蝇和哺乳动物中也可以作为治疗行为障碍（例如饮食失调和肥胖）的目标。