Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior

Area of Science:

• Neuroscience
• Microbiology
• Genetics

Background:

• Gene-environment interactions are crucial in neuropsychiatric disorders.
• The specific role of the gut microbiota in these interactions remains unclear.

Purpose of the Study:

• To investigate if gut microbiota alone can induce depressive-like behaviors.
• To explore the mechanisms by which gut microbiota influences social behavior and brain function.

Main Methods:

• Inducing depressive-like behaviors in mice via gut microbiota manipulation.
• Utilizing antibiotic treatment to deplete gut microbiota.
• Performing microbiota transfer experiments between genetically distinct mouse strains.
• Analyzing gene expression, myelination, and metabolite levels in the prefrontal cortex.

Main Results:

• Gut microbiota from specific mouse strains was sufficient to induce social avoidance behavior.
• Microbiota transfer altered gene expression and myelination in the recipient mice's prefrontal cortex.
• Increased cresol levels were identified, and this metabolite impaired myelin gene expression in vitro.

Conclusions:

• Gut microbiota plays a causal role in modulating social behavior and brain characteristics.
• Gut microbiota influences the synthesis of metabolites that affect gene expression and myelination.
• These findings establish a direct link between gut microbiota composition and neuropsychiatric disorder phenotypes.