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Published on: February 3, 2016
Fecal microbiota transplantation improves VPA-induced ASD mice by modulating the serotonergic and glutamatergic
Jifeng Wang1, Yuan Cao1, Weiliang Hou2
1Department of Pathology, Shanghai Tenth People's Hospital Affiliated to Tongji University, 200072, Shanghai, China.
Abstract:
Autism spectrum disorder (ASD) is a complex behavioral disorder diagnosed by social interaction difficulties, restricted verbal communication, and repetitive behaviors. Fecal microbiota transplantation (FMT) is a safe and efficient strategy to adjust gut microbiota dysbiosis and improve ASD-related behavioral symptoms, but its regulatory mechanism is unknown. The impact of the microbiota and its functions on ASD development is urgently being investigated to develop new therapeutic strategies for ASD. We reconstituted the gut microbiota of a valproic acid (VPA)-induced autism mouse model through FMT and found that ASD is in part driven by specific gut dysbiosis and metabolite changes that are involved in the signaling of serotonergic synapse and glutamatergic synapse pathways, which might be associated with behavioral changes. Further analysis of the microbiota showed a profound decrease in the genera Bacteroides and Odoribacter, both of which likely contributed to the regulation of serotonergic and glutamatergic synapse metabolism in mice. The engraftment of Turicibacter and Alistipes was also positively correlated with the improvement in behavior after FMT. Our results suggested that successful transfer of the gut microbiota from healthy donors to ASD mice was sufficient to improve ASD-related behaviors. Modulation of gut dysbiosis by FMT could be an effective approach to improve ASD-related behaviors in patients.
Insights
Fecal microbiota transplantation (FMT) can improve autism spectrum disorder (ASD) behaviors by restoring gut bacteria. This study shows FMT normalizes gut microbes, impacting brain signaling pathways and reducing ASD symptoms in mice.
Area of Science:
- Neuroscience
- Microbiology
- Genetics
Background:
- Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social interaction deficits, communication challenges, and repetitive behaviors.
- Gut microbiota dysbiosis is increasingly implicated in ASD pathogenesis, but the underlying mechanisms remain unclear.
- Fecal microbiota transplantation (FMT) shows promise for modulating gut microbiota and potentially alleviating ASD symptoms.
Purpose of the Study:
- To investigate the regulatory mechanisms of FMT in a valproic acid (VPA)-induced mouse model of ASD.
- To identify specific gut microbial and metabolic changes associated with ASD and their impact on neurological pathways.
- To evaluate the efficacy of FMT in improving ASD-related behaviors.
Main Methods:
- Reconstitution of gut microbiota in VPA-induced ASD mice using FMT from healthy donors.
- Analysis of microbial composition and associated metabolic changes.
- Behavioral assessments to evaluate ASD-related symptoms post-FMT.
Main Results:
- FMT significantly improved ASD-related behaviors in the mouse model.
- ASD was associated with specific gut dysbiosis, including decreased abundance of Bacteroides and Odoribacter.
- Changes in microbial metabolites were linked to alterations in serotonergic and glutamatergic synapse signaling pathways.
- Engraftment of Turicibacter and Alistipes correlated with behavioral improvements.
Conclusions:
- Gut microbiota dysbiosis contributes to ASD pathogenesis through alterations in neuroactive metabolite signaling.
- FMT is a viable therapeutic strategy for improving ASD-related behaviors by restoring gut microbial balance.
- Targeting gut microbiota through FMT offers a promising avenue for novel ASD treatments.
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