Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice

Gil Sharon, Nikki Jamie Cruz, Dae Wook Kang, Michael J. Gandal, Bo Wang, Young Mo Kim, Erika M. Zink, Cameron P. Casey, Bryn C. Taylor, Christianne J. Lane, Lisa M. Bramer, Nancy G. Isern, David W. Hoyt, Cecilia Noecker, Michael J. Sweredoski, Annie Moradian, Elhanan Borenstein, Janet K. Jansson, Rob Knight, Thomas O. MetzCarlos Lois, Daniel H. Geschwind, Rosa Krajmalnik-Brown, Sarkis K. Mazmanian

Research output: Contribution to journalArticlepeer-review

180 Scopus citations

Abstract

Autism spectrum disorder (ASD) manifests as alterations in complex human behaviors including social communication and stereotypies. In addition to genetic risks, the gut microbiome differs between typically developing (TD) and ASD individuals, though it remains unclear whether the microbiome contributes to symptoms. We transplanted gut microbiota from human donors with ASD or TD controls into germ-free mice and reveal that colonization with ASD microbiota is sufficient to induce hallmark autistic behaviors. The brains of mice colonized with ASD microbiota display alternative splicing of ASD-relevant genes. Microbiome and metabolome profiles of mice harboring human microbiota predict that specific bacterial taxa and their metabolites modulate ASD behaviors. Indeed, treatment of an ASD mouse model with candidate microbial metabolites improves behavioral abnormalities and modulates neuronal excitability in the brain. We propose that the gut microbiota regulates behaviors in mice via production of neuroactive metabolites, suggesting that gut-brain connections contribute to the pathophysiology of ASD. Repetitive and social behavioral abnormalities in mice with microbiomes from patients with autism spectrum disorder can be corrected by the administration of specific metabolites.

Original languageEnglish (US)
Pages (from-to)1600-1618.e17
JournalCell
Volume177
Issue number6
DOIs
StatePublished - May 30 2019

Keywords

  • autism
  • autism spectrum disorder
  • bacterial metabolites
  • gut microbiome
  • gut-brain axis
  • metabolome
  • microbiota
  • mouse model

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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