Murine maternal microbiome modifies adverse effects of protein undernutrition on offspring neurobehaviour

Area of Science:

• Developmental biology
• Neuroscience
• Microbiome research

Background:

• Protein undernutrition in children impairs growth and neurodevelopment.
• The specific influences of timing, environment, and maternal factors on these outcomes remain unclear.

Purpose of the Study:

• To investigate the impact of prenatal protein restriction on offspring neurobehavioral development.
• To elucidate the roles of fetal development, maternal physiology, and the maternal microbiome in mediating these effects.

Main Methods:

• Utilized a mouse model of fetal growth restriction induced by maternal protein limitation during pregnancy.
• Employed cross-fostering experiments to differentiate maternal versus neonatal influences.
• Analyzed maternal gut microbiome, immune, milk, and serum metabolomic profiles.
• Examined fetal brain transcriptomic and metabolomic profiles.
• Administered a metabolite cocktail to dams to assess intervention effects.

Main Results:

• Adult offspring of protein-restricted dams exhibited cognitive and anxiety-like behavioral abnormalities.
• Behavioral impairments required both fetal programming and maternal peripartum physiological conditioning.
• Maternal gut microbiome diversity decreased, with altered maternal and fetal metabolomic profiles.
• Specific microbiome-dependent metabolites were identified in fetal brain changes.
• Dam treatment with specific metabolites differentially affected fetal development and postnatal behavior.

Conclusions:

• Prenatal maternal protein undernutrition significantly impacts offspring neurobehavioral trajectories.
• The maternal microbiome and associated metabolic changes play a crucial role in mediating these effects.
• Both fetal programming and maternal physiological adaptations are essential for the observed neurobehavioral outcomes.