Unraveling gut-microbiome-brain interactions in neurodevelopmental disorders

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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.