Alisa had to pack up and move while she was eight months pregnant—a stressful undertaking even without bearing an extra 25 pounds and an inability to tie her own shoes. But luckily, her best friend stepped in. As Alisa reports, “My bestie helped to pack up well over half my house as well as scrubbed the [entire] new home we moved into!”

Offering to pack up a pregnant women’s household to help her stay calm might seem a little over the top. But according to Eldin Jašarević, a fourth-year postdoctoral fellow in the lab of Tracy L. Bale at the University of Pennsylvania, certain stressors during pregnancy might be no trivial matter.

Part of Jašarević’s work in the Bale lab is to look at the factors affecting the mental health of an animal as it develops in its mother’s womb and continues to develop through its lifetime.

A line of evidence in animals suggests certain stressors during pregnancy interfere with the offspring’s normal brain development

In an interview with GMFH editors, Jašarević says a line of evidence in animals suggests certain stressors during pregnancy interfere with the normal brain development of the offspring—especially male offspring—and these stressors could have this effect, in part, by altering which microorganisms reside in the gut.

Jašarević describes a study published earlier this year in which he and colleagues used a mouse model to test the effects of stress in pregnancy. “We exposed pregnant mice during the first week to a variety of different stressors that vary in frequency, duration, and chronicity,” he explains. “It’s really supposed to model the unexpected, unpredictable, uncontrollable stressors that most of us experience.”

From previous work, they knew that stressing the pregnant mice in this way would affect the brain health of their male offspring: by adulthood, these males would develop unusual responses to stressors they themselves encountered, and several other cognitive abnormalities.

The researchers wanted to know if the stress had any impact on the normal progression of gut bacterial change during the mouse mothers’ 19-day gestation period. “We took fecal samples every day. We looked at microbial community composition across time,” says Jašarević. “What we saw was that stress indeed disrupts that natural patterning of the gut microbiota during pregnancy.”

He continues, “Not only does it affect, at the compositional level, ‘who’s in there’, but it also affects ‘what are they doing?’” The disruption was observed not only in the gut microbiota of the mother mice, but also in their vaginal microbiota.

Jašarević and his colleagues suspect that the availability of nutrients, as buffered somehow by the gut microbiota, could affect how the youngsters’ immune systems and brains develop. Essentially, gut microbiota disruption may influence maternal nutritional status—the mother’s ability to ‘harvest’ nutrients from her diet—and thus change the energy supplies available to the brain of the developing offspring. Interactions with hormones could explain the specific effects on male mice.

When it comes to humans, the story is still unfolding, however. Jašarević notes, “We’re trying to now take what we know in the mouse setting and trying to adapt this—from bedside to bench, back to bedside.”

Although he can’t yet say if the situation for humans will be exactly the same, Jašarević points to well-known data from the Dutch Hunger Winter famine and other studies showing that a mother’s nutritional status is critical for the brain development of her children.

“Now what we’re adding is this new component, this new complex layer,” he explains. “Yes, the nutritional status really matters, but it appears that the nutritional status seems to be mediated by the gut microbiota that’s present in mom.”

Jašarević points out, “Many nutrients that support normal fetal growth are provided by mom, and many of these nutrients are of microbial origin—short chain fatty acids, among others.”

“It’s quite fascinating that you have an intimate interaction between diet, mom’s gut microbiota, then potentially the development of the fetus,” he says.

“We’re coming around to understanding this idea of the microbiome, particularly mom’s microbiome during pregnancy, or during the early postpartum/lactation period, being important for normal development—but also being important for neural development.”

 

 

Reference:

Jašarević E, Howard CD, Misic AM, Beiting DP, Bale TL. Stress during pregnancy alters temporal and spatial dynamics of the maternal and offspring microbiome in a sex-specific manner. Scientific Reports. 2017; 7:44182. doi: 10.1038/srep44182