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

By G. Sharon, Nikki Jamie Cruz, Dae-Wook Kang, Michael Jeffrey Gandal, Bo Wang, Young-Mo Kim, Erika M. Zink, Cameron P. Casey, Bryn C. Taylor, C. Lane and 14 more. Cell, 2019

1,004 citations recorded by the source corpus.

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.

Subfields: Cognitive Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/afd469685e7754bfd52bfa454d808bbbec849f79

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In Molecular Biology

Citations in the corpus

Gut Microbiome: Profound Implications for Diet and Disease (2019, background): “Future research will need to characterize the changes in bacterial composition accompanying different disease states and the corresponding expression patterns in genes of both microbe and host [296,300].”
The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020, background): “Recently, Sharon and collaborators showed that microbiota transplantation from human ASD donors into mice could transfer ASD-relevant behavioral deficits (27).”