Mechanisms Underlying Microbial-Mediated Changes in Social Behavior in Mouse Models of Autism Spectrum Disorder

Area of Science:

• Neuroscience
• Microbiology
• Genetics

Background:

• Autism Spectrum Disorder (ASD) presents core social deficits with no current effective pharmaceutical treatments.
• Previous research indicated Lactobacillus (L.) reuteri may ameliorate social deficits in specific ASD models.
• The generalizability and underlying mechanisms of L. reuteri's effects on social behavior in ASD remained unexplored.

Purpose of the Study:

• To investigate the efficacy of L. reuteri in diverse Autism Spectrum Disorder (ASD) models.
• To elucidate the mechanism of action by which L. reuteri influences social behavior in ASD.

Main Methods:

• Treatment of genetic, environmental, and idiopathic Autism Spectrum Disorder (ASD) mouse models with L. reuteri.
• Analysis of gut microbiome composition.
• Assessment of vagus nerve dependency.
• Measurement of synaptic plasticity in the ventral tegmental area.

Main Results:

• L. reuteri selectively rescued social deficits across multiple ASD models.
• The therapeutic effects were independent of restoring gut microbiome composition.
• L. reuteri's action was dependent on the vagus nerve.
• Synaptic plasticity in the ventral tegmental area was restored in ASD mice treated with L. reuteri.

Conclusions:

• L. reuteri demonstrates broad efficacy in ameliorating social deficits in various Autism Spectrum Disorder (ASD) models.
• The mechanism involves vagus nerve signaling and impacts synaptic plasticity, not gut microbiome restoration.
• L. reuteri represents a promising non-invasive, microbial-based therapeutic strategy for ASD-related social dysfunction.