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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