Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring

Shelly Buffington, Gonzalo Viana Di Prisco, Thomas A. Auchtung, Nadim J. Ajami, Joseph F. Petrosino, Mauro Costa-Mattioli

Research output: Contribution to journalArticle

226 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1762-1775
Number of pages14
JournalCell
Volume165
Issue number7
DOIs
StatePublished - Jun 16 2016
Externally publishedYes

Fingerprint

Nutrition
Mothers
Diet
High Fat Diet
Fats
Ventral Tegmental Area
Oxytocin
Dysbiosis
Metagenomics
Ecology
Social Behavior
Microbiota
Probiotics
Interpersonal Relations
Neurons
Plasticity
Hypothalamus
Obesity
Pregnancy

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Buffington, S., Di Prisco, G. V., Auchtung, T. A., Ajami, N. J., Petrosino, J. F., & Costa-Mattioli, M. (2016). Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring. Cell, 165(7), 1762-1775. https://doi.org/10.1016/j.cell.2016.06.001

Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring. / Buffington, Shelly; Di Prisco, Gonzalo Viana; Auchtung, Thomas A.; Ajami, Nadim J.; Petrosino, Joseph F.; Costa-Mattioli, Mauro.

In: Cell, Vol. 165, No. 7, 16.06.2016, p. 1762-1775.

Research output: Contribution to journalArticle

Buffington, S, Di Prisco, GV, Auchtung, TA, Ajami, NJ, Petrosino, JF & Costa-Mattioli, M 2016, 'Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring', Cell, vol. 165, no. 7, pp. 1762-1775. https://doi.org/10.1016/j.cell.2016.06.001
Buffington S, Di Prisco GV, Auchtung TA, Ajami NJ, Petrosino JF, Costa-Mattioli M. Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring. Cell. 2016 Jun 16;165(7):1762-1775. https://doi.org/10.1016/j.cell.2016.06.001
Buffington, Shelly ; Di Prisco, Gonzalo Viana ; Auchtung, Thomas A. ; Ajami, Nadim J. ; Petrosino, Joseph F. ; Costa-Mattioli, Mauro. / Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring. In: Cell. 2016 ; Vol. 165, No. 7. pp. 1762-1775.
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