Researchers from the University of Pennsylvania have found for the first time that stress during the first trimester of pregnancy alters the population of microbes living in a mother’s vagina. Those changes are passed on to newborns during birth and are associated with differences in their gut microbiome as well as their brain development state the team. The study is published in the journal Endocrinology.
Previous studies show that during a vaginal birth, a newborn is exposed to its mother’s vaginal microbes, collectively known as the microbiota, which importantly colonizes the newborn’s gut, helping its immune system mature and influencing its metabolism. These effects take place during a critical window of brain development. Babies born by C-section miss out on this initial exposure and are more likely to be exposed to and their guts then colonized by other bacteria in the local environment, including the mother’s skin and potential pathogens in the hospital.
The current study suggests that the maternal vaginal microbiome is one of the ways that a mother’s stress during pregnancy can ‘reprogram’ the developing brains of her children. The team state that one implication is that these changes could put the offspring at an increased risk of neurodevelopment disorders such as autism and schizophrenia, neurodevelopmental disorders where disruption of gut microbiota and gastrointestinal dysfunction are increasingly reported.
The researchers explain that a mother’s stress during pregnancy can impact her offspring’s development, including the brain, through changes in the vaginal microbiome that are passed on during vaginal birth. As the neonate’s gut is initially populated by the maternal vaginal microbiota, changes produced by maternal stress can alter this initial microbial population as well as determine many aspects of the host’s immune system that are also established during this early period.
The current study used a mouse model of early maternal stress that the lab had previously developed. An experimental group of pregnant mice were periodically exposed to stressors, such as predator odors, restraint and novel noises, early in gestation, the equivalent of their ‘first trimester.’ The day following birth, the team assessed the microbiota from the mothers’ vaginas and from the offsprings’ colons. In addition, the offsprings’ brains were examined to measure transport of amino acids, a proxy for brain metabolism and development.
The data findings showed that stress during early pregnancy had surprising long-lasting effects on the mother’s vaginal microbiota. The team observed that these changes were reflected in their offspring’s gut microbiota and were associated with alterations in the offspring’s metabolism and amino acid processing in the brain. The neurodevelopmental effects were particularly pronounced in male mice, which is the sex that the lab have previously demonstrated shows a stress-sensitive phenotype later in life.
The researchers note that taken together these results not only underscore the important role that the mother’s vaginal microbiome has in populating her offspring’s gut at birth but also the profound effect of maternal stress experience on this microbial population and on early gut and brain development. The fact that male offspring appeared most affected may have implications for the development of disorders such as autism and schizophrenia, both of which disproportionately affect males.
Interestingly, the team add that a subset of offspring that were delivered by C-section and then had their mother’s vaginal microbiota introduced to their gut ultimately had gut microbiota that resembled that of vaginally-delivered offspring.
The team surmise that these studies have enormous translational potential. They go on to add that many countries are already administering oral application of vaginal lavages to C-section delivered babies to ensure appropriate microbial exposure occurs. The researchers stress that knowledge of how maternal experiences such as stress during pregnancy can alter the vaginal microbiome is critical in determination of at-risk populations and needs further investigation.
Source: University of Pennsylvania
