Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring.
Maternal obesity during pregnancy has been associated with increased risk of neurodevelopmental disorders, including autism spectrum disorder (ASD), in offspring. Here, we report that maternal high-fat diet (MHFD) induces a shift in microbial ecology that negatively impacts offspring social behavior. Social deficits and gut microbiota dysbiosis in MHFD offspring are prevented by co-housing with offspring of mothers on a regular diet (MRD) and transferable to germ-free mice. In addition, social interaction induces synaptic potentiation (LTP) in the ventral tegmental area (VTA) of MRD, but not MHFD offspring. Moreover, MHFD offspring had fewer oxytocin immunoreactive neurons in the hypothalamus. Using metagenomics and precision microbiota reconstitution, we identified a single commensal strain that corrects oxytocin levels, LTP, and social deficits in MHFD offspring. Our findings causally link maternal diet, gut microbial imbalance, VTA plasticity, and behavior and suggest that probiotic treatment may relieve specific behavioral abnormalities associated with neurodevelopmental disorders. VIDEO ABSTRACT.
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Memory and Brain Research Center, Baylor College of Medicine, Houston, TX 77030, USA.
Shelly A
SA
Buffington
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Memory and Brain Research Center, Baylor College of Medicine, Houston, TX 77030, USA.
Gonzalo Viana
GV
Di Prisco
Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Thomas A
TA
Auchtung
Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Nadim J
NJ
Ajami
Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Joseph F
JF
Petrosino
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Memory and Brain Research Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: costamat@bcm.edu.
Mauro
M
Costa-Mattioli
D000818:Animals; D000067877:Autism Spectrum Disorder / Q000382:microbiology*; D059305:Diet, High-Fat; D064806:Dysbiosis / Q000503:physiopathology; D005260:Female; D000069196:Gastrointestinal Microbiome; D005856:Germ-Free Life; D006799:Housing, Animal; D052200:Limosilactobacillus reuteri; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications*; D010121:Oxytocin / Q000032:analysis / Q000378:metabolism; D011247:Pregnancy; D012919:Social Behavior; D017557:Ventral Tegmental Area
D010121:Oxytocin
autism; dysbiosis; high-fat diet (HFD); long-term potentiation (LTP); neurodevelopmental disorders; probiotic; ventral tegmental area (VTA)