Mom’s diet matters: effects of mouse maternal prebiotic intake on the offspring brain and behaviour

Background: Studies are increasingly pointing to the gut microbiome as an important modulator of brain development and function. The galacto-oligosaccharide prebiotic Bimuno® (BGOS) has been shown to alter behaviour and brain gene expression in rodents when administered orally during both early life and adulthood. BGOS also influences gut microbiome composition, production of short-chain fatty acids (SCFAs) through fermentation, and host immune function and metabolism. In addition, the maternal microbiome is important for offspring brain and behaviour development. Therefore, BGOS supplementation during pregnancy and lactation in mice may modulate the maternal gut microbiome and, in turn, influence offspring behaviour and brain gene expression.
Methods: CD1 dams were randomly assigned to receive either normal drinking water or drinking water supplemented with BGOS during gestation and suckling. Offspring were tested at weaning age or adulthood, and a cross-foster design was employed in a separate cohort to differentiate between effects of prenatal and postnatal maternal BGOS intake. Acute or early-life lipopolysaccharide was also administered to determine whether maternal BGOS mitigates the brain and behaviour effects of a pro-inflammatory challenge. Exploratory, anxiety-like, and passive stress-coping behaviours were assessed. In the brain, relative gene expression of glutamate and serotonin receptors, brain-derived neurotrophic factor, and pro-inflammatory markers was quantified in the prefrontal cortex and hippocampus. To explore mechanisms that may underlie changes in the offspring brain and behaviour, immune cell composition and function and host plasma metabolite profiles were also assessed in offspring. Finally, maternal and offspring faecal microbiome diversity, composition, and metabolites were analysed to explore potential relationships between the maternal microbiome, the offspring gut microbiome, and the offspring brain, behaviour, immunity, and metabolism.
Results: Maternal BGOS supplementation during gestation and suckling increased exploratory behaviour and reduced anxiety and behavioural despair in young CD1 offspring at weaning age. In cross-fostered pups, both prenatal and postnatal maternal BGOS increased exploration, while postnatal BGOS additionally reduced anxious behaviour. Maternal BGOS also reduced expression of cortical and hippocampal glutamate and serotonin receptor genes in young offspring. In addition, immune cell composition and function and plasma metabolite profiles were altered. In adult offspring, perinatal BGOS induced long-lasting and sex-dependent changes in behaviour, brain gene expression, and plasma metabolites. Finally, while offspring faecal microbiome beta diversity, composition, and metabolite profiles were significantly different in young BGOS pups compared to controls, including increased levels of SCFAs, minimal microbial changes were detected in maternal faecal samples. Differentially abundant taxa, but not faecal metabolites, correlated with changes in offspring behaviour and gene expression.
Conclusion: Maternal BGOS produced long-lasting changes in behaviour and brain gene expression in young and adult offspring. These differences were accompanied by changes in plasma metabolite profiles and immune function. Although differences in beta diversity and abundances of specific taxa were detected in offspring faecal samples, BGOS did not substantially alter the maternal faecal bacteria. This suggests that maternal BGOS-induced changes in the offspring brain and behaviour are independent of changes in the maternal microbiome. Therefore, future studies will need to explore how maternal BGOS intake changes the offspring gut microbiome and whether there is a causal relationship between the offspring microbiome and brain and behaviour changes.

Keywords: maternal diet
16S
NMR
prebiotics
gut microbiome
NMDA
Advisor: Burnet, P
Anthony, D