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Microbiota-Based Interventions Differentially Rescue Gut and Social Behavior Phenotypes in Drosophila with Kdm5
Developmental Neuroscience
|May 21, 2026
Summary
Disrupting the ASD-associated gene KDM5 impacts gut microbes and social behavior in flies. While restoring microbes helped, only specific strains like L. helveticus improved social interaction, showing functional host-microbe interactions are key.
Area of Science:
- Neuroscience
- Microbiology
- Genetics
Background:
- Autism spectrum disorder (ASD) is linked to gastrointestinal (GI) issues, potentially mediated by the gut microbiota-brain axis.
- Loss-of-function mutations in KDM5 histone demethylases are associated with intellectual disability and ASD.
- Previous studies in Drosophila showed Kdm5 loss-of-function (Kdm5LOF) causes gut dysbiosis and impaired social behavior, with L. plantarum failing to restore social function.
Purpose of the Study:
- To investigate how disrupting the ASD-associated gene KDM5 affects gut microbial composition and social behavior using a Drosophila model.
- To evaluate the efficacy of various microbiota-based interventions, including probiotics and fecal microbiota transplantation (FMT), in modulating gut microbiota and behavior in Kdm5LOF flies.
Main Methods:
- Assessed gut bacterial abundance using colony-forming unit (CFU) assays and 16S rRNA gene sequencing.
- Evaluated social behavior via social distance assays and anxiety-like behavior/locomotion using open field tests.
- Utilized gut-specific Kdm5 knockdown and FMT to dissect tissue-specific roles and microbial community effects.
Main Results:
- Kdm5 deficiency reduced specific gut bacteria (Lactobacillus, Acetobacter, Enterobacter) and impaired social behavior.
- L. plantarum restored microbial abundance but not social behavior; L. helveticus improved social interaction with minimal microbial changes.
- FMT partially restored gut microbes and social behavior in Kdm5LOF flies, indicating strain-specific and phenotype-specific intervention effects.
Conclusions:
- KDM5 is crucial for maintaining gut microbial viability and social behavior.
- Microbiota restoration alone is insufficient for behavioral rescue; functional host-microbe interactions are vital.
- Drosophila serves as a model for studying epigenetic regulation of microbiota-behavior links and microbiota-based interventions.
