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Published on: June 2, 2022
Behavioral and biological alterations following transplantation of ASD-associated gut microbiota in mice
Yang Gao1, Dan Yang1, Danni Wang1
1The First Affiliated Hospital, Xinjiang Medical University, Urumqi, China.
Background:
Alterations in the gut microbiota have been increasingly reported in individuals with autism spectrum disorder (ASD). However, the extent to which ASD-associated microbial communities are linked to behavioral and host biological changes remains to be clarified.
Methods:
Fecal microbiota transplantation (FMT) was performed using samples from children with ASD or typically developing (TD) controls into antibiotic-pretreated mice. Behavioral performance was evaluated using open field, social interaction, and spatial learning paradigms. Gut microbial composition was assessed by 16S rRNA gene sequencing. Peripheral immune-related parameters were assessed, including circulating regulatory T cells and serum cytokine profiles. Histological and molecular analyses were conducted in the terminal ileum and hippocampus, including immunohistochemistry, Western blotting, exploratory brain proteomics, and targeted qRT-PCR validation.
Results:
Mice receiving ASD-associated microbiota displayed altered behavioral performance, including reduced sociability and impaired spatial learning. 16S rRNA sequencing revealed distinct gut microbial profiles between ASD-FMT and TD-FMT groups, with increased abundance of Enterobacteriaceae and related taxa in ASD-FMT mice. Peripheral analysis showed reduced regulatory T cell levels and altered serum cytokine profiles. Histological examination identified changes in intestinal architecture and increased expression of glial markers in the hippocampus. Proteomic analysis indicated differential expression of proteins enriched in pathways related to neural structural organization and metabolic processes.
Conclusions:
These findings indicate that gut microbiota derived from children with ASD is associated with coordinated behavioral, peripheral immune-related, and brain histological changes in mice. This study provides integrative evidence supporting associations between ASD-associated microbial features and coordinated behavioral and biological alterations in the host.
Insights
Gut microbes from children with autism spectrum disorder (ASD) altered mouse behavior and biology. This research links ASD-associated gut bacteria to changes in social interaction, learning, immunity, and brain structure.
Area of Science:
- Microbiome research
- Neuroscience
- Immunology
Background:
- Gut microbiota alterations are increasingly reported in autism spectrum disorder (ASD).
- The precise link between ASD-associated microbial communities and host behavioral/biological changes requires clarification.
Purpose of the Study:
- To investigate the impact of gut microbiota from children with ASD on host behavior and biology in a mouse model.
- To explore the relationship between ASD-associated gut microbes and host immune and neural changes.
Main Methods:
- Fecal microbiota transplantation (FMT) from ASD children or typically developing (TD) controls into mice.
- Behavioral testing (open field, social interaction, spatial learning), 16S rRNA gene sequencing for gut microbiota analysis.
- Assessment of peripheral immune markers, serum cytokines, and histological/molecular analyses of the ileum and hippocampus.
Main Results:
- Mice receiving ASD microbiota showed reduced sociability and impaired spatial learning.
- Distinct microbial profiles, including increased Enterobacteriaceae, were observed in ASD-FMT mice.
- Reduced regulatory T cells, altered cytokines, intestinal changes, and increased hippocampal glial markers were noted.
Conclusions:
- Gut microbiota from children with ASD is associated with coordinated behavioral, immune, and brain changes in mice.
- This study provides evidence linking ASD-associated microbial features to host biological alterations.
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