Maternal immune activation and antibiotics affect offspring neurodevelopment, behaviour, and microbiome

Area of Science:

• Neuroscience
• Developmental Biology
• Microbiome Research

Background:

• Maternal inflammation and gut microbiome alterations during pregnancy are linked to offspring neurodevelopmental disorders.
• The interaction between maternal immune activation (MIA) and the maternal gut microbiome in influencing neurodevelopmental outcomes is understudied.

Purpose of the Study:

• To investigate if maternal gut microbiome disruption exacerbates the effects of systemic inflammation on offspring brain development, behavior, and long-term microbiome composition.
• To explore the combined impact of prenatal inflammation and microbiome dysbiosis on neurodevelopmental trajectories.

Main Methods:

• Pregnant Sprague Dawley rats received low-dose lipopolysaccharide (LPS) and an antibiotic cocktail to induce systemic inflammation and gut microbiome disruption, respectively.
• Embryonic development, offspring behavior (anxiety-like and repetitive behaviors), prefrontal cortex 5HT1a receptor expression, and microbiome composition were assessed.

Main Results:

• Prenatal LPS exposure led to reduced embryonic body and placental weight, increased offspring anxiety-like and repetitive behaviors, and decreased 5HT1a receptor expression in the prefrontal cortex.
• Antibiotic exposure alone did not cause behavioral changes but reduced offspring microbiome alpha-diversity and species richness.
• Combined exposures showed exacerbated effects on neurodevelopmental and microbiome parameters.

Conclusions:

• Prenatal exposure to inflammation and gut microbiome disruption significantly impacts offspring neurodevelopment and long-term health.
• Maternal immune activation and microbiome status interact to influence offspring neurodevelopmental outcomes.
• Further research into therapeutic interventions like probiotics is warranted to mitigate these adverse prenatal effects.