As in humans, the mouse gut is home to an incredible number and variety of microbial life. Research conducted in the past decade has established that the gut microbiota has far-reaching effects on the rest of the body – for example it can modify immune function, influence brain chemistry, and transform behaviour. The way in which gut microbes can exert these effects is by the modification of our blood chemistry by mixing their metabolites with our own.
In a new study, University of Oxford scientists report that alterations to the maternal gut microbiota through a high-fat diet not only affects the gut metabolite composition of the mother, but pervasively affect the gut and brain metabolism and anxiety-like behaviour of the adult offspring. The behavioural change was prevented by providing the pregnant mice with a probiotic supplement during the critical period of foetal brain development.
The researchers used a combination of gene-expression analysis and metabolomics (a method to quantify metabolites in a biological sample) to determine which specific factors were associated with these changes in behaviour.
The results showed that administration of the probiotic to the mother significantly elevated the abundance of neuroactive metabolites in the gut and milk of the mothers during nursing. Some of these metabolites were also elevated in the offspring from mothers given the supplement, suggesting that modification of the maternal microbiota during pregnancy has direct and long-lasting effects on offspring metabolism. Elevated levels of brain lactate, a neuroactive substance, were correlated with reduced anxiety-like behaviour, suggesting that this molecule may be the source of the remedial effects of early-life probiotic exposure. The metabolic activity of cells in the brain called astrocytes, which are the equivalent of carers for neurons, was also enhanced by the treatment.
Daniel Radford-Smith, researcher on the study from the University of Oxford, says: ‘We were very surprised at how maternal probiotic treatment could instil such enduring changes in the offspring in relation to brain metabolism and behaviour. We don’t know to what extent these results may translate to humans; however, our study suggests that the maternal gut microbiota and associated metabolites should be considered, alongside established genetic and environmental risk factors, as potentially having an enduring effect on the health trajectory of the offspring.’
Maternal obesity is a growing public health concern and is linked to an increased risk of neurodevelopmental and psychiatric disorders in humans. Professor Daniel Anthony, at the University of Oxford, also commented: ‘Pharmacotherapy during pregnancy often raises safety concerns. The use of probiotics represents a safe alternative that appears to have real promise for mitigating the effects of maternal obesity on offspring neurodevelopment and behaviour.’
Future studies will aim to investigate whether individual strains of gut bacteria or metabolites are sufficient to reproduce the long-lasting effects on behavior and brain function in the offspring.
The full paper, ‘Modifying the maternal microbiota alters the gut-brain metabolome and prevents emotional dysfunction in the adult offspring of obese dams’, is available open-access in Proceedings of the National Academy of Sciences of the United States of America, a leading multidisciplinary journal with a global readership.
See the full paper at: https://www.pnas.org/content/119/9/e2108581119