TY - JOUR
T1 - Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring
AU - Buffington, Shelly A.
AU - Di Prisco, Gonzalo Viana
AU - Auchtung, Thomas A.
AU - Ajami, Nadim J.
AU - Petrosino, Joseph F.
AU - Costa-Mattioli, Mauro
N1 - Funding Information:
We thank members of the Costa-Mattioli laboratory, K. Krnjević, M. Beauchamp, and H. Dierick for comments on the manuscript; A. Swennes, J. Garcia, D. Quach and J. Auchtung for technical advice. This work was supported by funding from the NIH (NIMH 096816, NINDS 076708) to M.C.-M and the Alkek Foundation and Baylor College of Medicine to the Alkek Center for Metagenomics and Microbiome Research to J.F.P.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/6/16
Y1 - 2016/6/16
N2 - 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.
AB - 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.
KW - autism
KW - dysbiosis
KW - high-fat diet (HFD)
KW - long-term potentiation (LTP)
KW - neurodevelopmental disorders
KW - probiotic
KW - ventral tegmental area (VTA)
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U2 - 10.1016/j.cell.2016.06.001
DO - 10.1016/j.cell.2016.06.001
M3 - Article
C2 - 27315483
AN - SCOPUS:84975317355
SN - 0092-8674
VL - 165
SP - 1762
EP - 1775
JO - Cell
JF - Cell
IS - 7
ER -