Unraveling gut-microbiome-brain interactions in neurodevelopmental disorders

揭示神经发育障碍中肠道-微生物-大脑的相互作用

基本信息

批准号：
10666610
负责人：
Ergun Sahin
金额：
$ 65.3万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-16 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10666610
关键词：
Amaze Animals Area Behavior Behavioral Bilateral Brain Brain region Candidate Disease Gene Central Nervous System Diseases Complex DNA Sequence Alteration Data Development Dimensions Disease Dissection Electrophysiology (science)Engineering Environmental Risk Factor Etiology Exhibits FMR1 Fiber Generations Genes Genetic Genetic Models Genetic Screening Goals Impairment Individual Laboratories Lactobacillus reuteri Mediating Metagenomics Microbial Genetics Microbiology Modeling Molecular Mus Neurodevelopmental Disorder Neurons Neurosciences Oxytocin Pathway interactions Pharmacology Physiology Prevalence Probiotics Reproducibility Research Rewards Role Series Signal Pathway Signal Transduction Social Behavior Structure Synaptic plasticity System Testing Therapeutic Vagotomy Vagus nerve structure Work bacterial genetics commensal bacteria gain of function genetic makeup gut microbes gut microbiome gut microbiota gut-brain axis improved insight loss of function maternal obesity metabolomics microbial microbial based therapy microbiome alteration microorganism mouse model multidisciplinary novel offspring optogenetics prevent social social deficits synaptic function tetrahydrobiopterin transcriptome sequencing transcriptomics

项目摘要

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.

项目摘要目前神经发育障碍（NDD）研究的大部分重点都是基于确定关键的神经发育障碍（NDD）研究。引起明显行为和行为的大脑区域、相关信号通路和选择性大脑回路隐含的内部神经状态，我们最近发现特定的肠道微生物可以调节大脑在这里，我们将通过肠脑轴以一种令人惊讶的强大方式结合最新的功能和行为。转录组学、代谢组学、药理学、微生物学、遗传学、宏基因组学、电生理学和识别肠道微生物（罗伊氏乳杆菌）逆转 NDD 社交缺陷的机制的行为简而言之，我们将定义罗伊氏乳杆菌和罗伊氏乳杆菌的分子和遗传机制。此外，我们将确定诱导代谢物促进社会行为和突触功能的相关变化。罗伊氏乳杆菌和罗伊氏乳杆菌诱导代谢物的肠-脑通讯模式（“肠-脑轴”）最后，我们将评估罗伊氏乳杆菌更广泛的治疗潜力。我们的研究结果不仅可以为具有社交功能障碍的 NDD 模型提供诱导代谢物。肠道微生物如何控制行为和大脑的新整体维度，但它们也可能导致开发新的非侵入性微生物疗法来治疗 NDD。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mechanisms Underlying M icrobial-Mediated Changes in Social Behavior in Mouse Models of Autism Spectrum Disorder Graphical

自闭症谱系障碍小鼠模型中微生物介导的社会行为变化的机制图解

DOI：
发表时间：
2024-09-14
期刊：
影响因子：
0
作者：
M. Sgritta;Sean W. Dooling;Shelly A Buffington;E. Momin;Michael B. Francis;R. Britton;Mauro Costa
通讯作者：
Mauro Costa

Control of Cocaine Relapse: Lost in Translation.

控制可卡因复吸：迷失在翻译中。

DOI：
发表时间：
2018-08-01
期刊：
影响因子：
10.6
作者：
Sgritta; Martina
通讯作者：
Martina

The Effect of Limosilactobacillus reuteri on Social Behavior Is Independent of the Adaptive Immune System.

罗伊氏柠檬酸杆菌对社会行为的影响独立于适应性免疫系统。

DOI：
发表时间：
2022-12-20
期刊：
影响因子：
6.4
作者：
Dooling, Sean W;Sgritta, Martina;Wang, I;Duque, Ana Luiza Rocha Faria;Costa
通讯作者：
Costa

mTORC2, but not mTORC1, is required for hippocampal mGluR-LTD and associated behaviors.

海马 mGluR-LTD 和相关行为需要 mTORC2，而不是 mTORC1。

DOI：
发表时间：
2018
期刊：
影响因子：
25
作者：
Zhu, Ping Jun;Chen, Chien;Mays, Jacqunae;Stoica, Loredana;Costa
通讯作者：
Costa

Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring.

微生物重建可逆转母亲饮食引起的后代社交和突触缺陷。

DOI：
发表时间：
2016-06-16
期刊：
影响因子：
64.5
作者：
Buffington, Shelly A;Di Prisco, Gonzalo Viana;Auchtung, Thomas A;Ajami, Nadim J;Petrosino, Joseph F;Costa
通讯作者：
Costa