Cell
Volume 165, Issue 7, 16 June 2016, Pages 1762-1775
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Article
Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring

https://doi.org/10.1016/j.cell.2016.06.001Get rights and content
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Highlights

  • Maternal high-fat diet (MHFD) induces behavioral alterations in offspring

  • MHFD causes alterations in gut microbial ecology in offspring

  • MHFD offspring show deficient synaptic plasticity in the VTA and oxytocin production

  • L. reuteri treatment restores oxytocin levels, VTA plasticity and social behaviors

Summary

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.

Keywords

neurodevelopmental disorders
autism
dysbiosis
high-fat diet (HFD)
ventral tegmental area (VTA)
long-term potentiation (LTP)
probiotic

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