Dysbiosis of microbiome and probiotic treatment in a genetic model of autism spectrum disorders

Laure Tabouy, Dimitry Getselter, Oren Ziv, Marcela Karpuj, Timothée Tabouy, Iva Lukic, Rasha Maayouf, Nir Werbner, Hila Ben-Amram, Meital Nuriel-Ohayon, Omry Koren, Evan Elliott

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

Recent studies have determined that the microbiome has direct effects on behavior, and may be dysregulated in neurodevelopmental conditions. Considering that neurodevelopmental conditions, such as autism, have a strong genetic etiology, it is necessary to understand if genes associated with neurodevelopmental disorders, such as Shank3, can influence the gut microbiome, and if probiotics can be a therapeutic tool. In this study, we have identified dysregulation of several genera and species of bacteria in the gut and colon of both male and female Shank3 KO mice. L. reuteri, a species with decreased relative abundance in the Shank3 KO mice, positively correlated with the expression of gamma-Aminobutyric acid (GABA) receptor subunits in the brain. Treatment of Shank3 KO mice with L. reuteri induced an attenuation of unsocial behavior specifically in male Shank3 mice, and a decrease in repetitive behaviors in both male and female Shank3 KO mice. In addition, L. reuteri treatment affected GABA receptor gene expression and protein levels in multiple brain regions. This study identifies bacterial species that are sensitive to an autism-related mutation, and further suggests a therapeutic potential for probiotic treatment.

Original languageEnglish
Pages (from-to)310-319
Number of pages10
JournalBrain, Behavior, and Immunity
Volume73
DOIs
StatePublished - Oct 2018

Bibliographical note

Publisher Copyright:
© 2018 Elsevier Inc.

Keywords

  • Autism
  • GABA
  • L. reuteri
  • Microbiome

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