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

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 contrib...

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Bibliographic Details
Published in:Cell 2019-05, Vol.177 (6), p.1600-1618.e17
Main Authors: Sharon, Gil, Cruz, Nikki Jamie, Kang, Dae-Wook, Gandal, Michael J., Wang, Bo, Kim, Young-Mo, Zink, Erika M., Casey, Cameron P., Taylor, Bryn C., Lane, Christianne J., Bramer, Lisa M., Isern, Nancy G., Hoyt, David W., Noecker, Cecilia, Sweredoski, Michael J., Moradian, Annie, Borenstein, Elhanan, Jansson, Janet K., Knight, Rob, Metz, Thomas O., Lois, Carlos, Geschwind, Daniel H., Krajmalnik-Brown, Rosa, Mazmanian, Sarkis K.
Format: Article
Language:English
Subjects:
Animals
autism
autism spectrum disorder
Autism Spectrum Disorder - metabolism
Autism Spectrum Disorder - microbiology
Autism Spectrum Disorder - physiopathology
Bacteria
bacterial metabolites
Behavior, Animal - physiology
Behavioral Symptoms - microbiology
Brain - metabolism
Disease Models, Animal
Gastrointestinal Microbiome - physiology
gut microbiome
gut-brain axis
Humans
metabolome
Mice
Microbiota
mouse model
Risk Factors
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Summary: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. [Display omitted] •Mice harboring human ASD, but not TD, microbiomes exhibit ASD-like behaviors•ASD and TD microbiota produce differential metabolome profiles in mice•Extensive alternative splicing of risk genes in brains of mice with ASD microbiota•BTBR mice treated with 5AV or taurine improved repetitive and social behaviors Repetitive and social behavioral abnormalities in mice with microbiomes from patients with autism spectrum disorder can be corrected by the administration of specific metabolites.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2019.05.004