The maternal microbiome modifies adverse effects of protein undernutrition on offspring neurobehavioral impairment in mice.

Consistent with this, maternal protein restriction during pregnancy reduces the diversity of the maternal gut microbiome, modulates maternal serum metabolomic profiles, and yields widespread alterations in fetal brain transcriptomic and metabolomic profiles, including subsets of microbiome-dependent metabolites. Further depletion of the maternal microbiome in protein-restricted dams exacerbates alterations in fetal brain gene expression and neurocognitive behavior in adult offspring, suggesting that the maternal microbiome modifies the impact of gestational protein undernutrition on risk for neurobehavioral impairment in the offspring.

To explore the potential for microbiome-targeted interventions, we find that maternal treatment with short chain fatty acids, a cocktail of 10 diet- and microbiome-dependent metabolites, or a consortium of gut bacteria reduced by protein undernutrition each yield differential effects on fetal development and/or postnatal behavior. Results from this study highlight impactful prenatal influences of maternal protein undernutrition on fetal neurodevelopment and adverse neurobehavioral trajectories in offspring, which are mitigated by microbiome-targeted interventions during pregnancy.