Unraveling gut-microbiome-brain interactions in neurodevelopmental disorders

项目摘要 目前神经发育障碍(NDDS)研究的大部分焦点都是基于确定关键的 大脑区域，相关的信号通路和选择性大脑回路，引起公开的行为和 内部神经元状态有趣的是，我们最近发现特定肠道微生物可以调节大脑 通过肠道-脑轴以一种令人惊讶的强大方式发挥功能和行为。在这里，我们将结合最新的- ART转录学、代谢组学、药理学、微生物学、遗传学、元基因组学、电生理学和 确定肠道微生物(L.reuri)逆转新城疫患者社会缺陷的机制的行为(S) 老鼠模型。简而言之，我们将定义路氏乳杆菌和路氏乳杆菌的分子和遗传机制。 诱导的代谢物促进社会行为和相关突触功能的变化。此外，我们将确定 路氏乳杆菌和路氏乳杆菌诱导代谢产物的肠脑通讯方式(‘肠脑轴’) 调节大脑功能和行为。最后，我们将评估路支杆菌的更广泛的治疗潜力- 社会功能障碍患者不同模型中诱导代谢产物的研究。我们的发现不仅可以提供一个 肠道微生物如何控制行为和大脑的新的整体维度，但它们也可能导致 以非侵入性微生物为基础的非侵入性新药的开发。

PROJECT ABSTRACT Most of the current focus in neurodevelopmental disorders (NDDs) research has been based on identifying key brain regions, relevant signaling pathways and selective brain circuits that give rise to overt behavioral and internal neuronal states Interestingly, we have recently found that that specific gut microbes can modulate brain function and behaviors in an amazingly powerful way via the gut-brain axis. Here we will combine state-of-the- art transcriptomics, metabolomics, pharmacology, microbiology, genetics, metagenomics, electrophysiology and behavior to identify the mechanism(s) by which a gut microbe (L. reuteri) reverses the social deficits in NDD mouse models. Briefly, we will define the molecular and genetic mechanism by which L. reuteri and L. reuteri- induced metabolites promote social behavior and related changes in synaptic function. In addition, we will identify the mode of gut-brain communication (‘gut-brain axis’) by which L. reuteri and L. reuteri-induced metabolites modulate brain function and behavior. Finally, we will assess the broader therapeutic potential for L. reuteri- induced metabolites in different models for NDDs with social dysfunction. Our findings could not only provide a new holistic dimension of how behaviors and the brain are controlled by gut microbes, but they could also lead to the development of new non-invasive microbial-based therapies for NDDs.