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      Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring

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          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.

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          Author and article information

          Journal
          0413066
          2830
          Cell
          Cell
          Cell
          0092-8674
          1097-4172
          22 June 2016
          16 June 2016
          16 June 2017
          : 165
          : 7
          : 1762-1775
          Affiliations
          [1 ]Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
          [2 ]Memory and Brain Research Center, Baylor College of Medicine, Houston, TX 77030, USA
          [3 ]Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX 77030, USA
          [4 ]Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
          Author notes
          [* ] Correspondence to: Mauro Costa-Mattioli ( costamat@ 123456bcm.edu )
          Article
          PMC5102250 PMC5102250 5102250 nihpa794301
          10.1016/j.cell.2016.06.001
          5102250
          27315483
          10cc3f47-1b99-4f6a-99b3-0ab329de7fac
          History
          Categories
          Article

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

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