Exposure to maternal obesity in utero perturbs the organization and maturation of the neural circuitry required for the development of a child?s mental health. In view of the concomitant increase in the prevalence of both obesity and Autism spectrum disorder (ASD), we crucially need to understand the relationship between the two. While maternal obesity significantly increases the risk of ASD in children, how maternal obesity leads to neurodevelopmental disorders in offspring remains unknown. By combining metagenomics, metabolomics, molecular biology, genetics, electrophysiology and behavioral studies both on conventionally colonized and on germ-free mice, we will test the hypothesis that maternal high fat diet (MHFD) induces a shift in microbial ecology which perturbs social behavior and related changes in synaptic strength in offspring. In addition, we will study the gut-brain axis and specific metabolites responsible for MHFD-mediated ASD-like behaviors in offspring. By defining the basic molecular and cellular mechanisms underlying MHFD-induced ASD, the knowledge gained in this study may also lead to new probiotic-based non-invasive treatments for millions of patients suffering from ASD.

Public Health Relevance

Maternal obesity increases the risk of Autism Spectrum Disorder (ASD), but the reason for this remains unclear. Here we will test the hypothesis that maternal obesity alters the gut bacterial content of their offspring, thus crucially perturbing their social behaviors. We will identify the bacterial strains (and metabolites) that are required for social behavior and related changes in synaptic strength; these studies could also lead to the development of novel probiotic-based non-invasive treatments for patients suffering from ASD and related disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH112356-02
Application #
9357706
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Winsky, Lois M
Project Start
2016-09-26
Project End
2021-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Neurosciences
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Zhu, Ping Jun; Chen, Chien-Ju; Mays, Jacqunae et al. (2018) mTORC2, but not mTORC1, is required for hippocampal mGluR-LTD and associated behaviors. Nat Neurosci 21:799-802
Petrosino, Joseph F (2018) The microbiome in precision medicine: the way forward. Genome Med 10:12