Why the Microbes in a Mother’s Gut Could Matter for a Developing Baby’s Brain

The Context: Scientists know that the microbes in a mother’s gut can affect brain function in offspring, usually in response to stress, infection, or other adverse conditions, but it is not known whether microbiota can shape brain development when mothers aren’t experiencing one of these conditions.

The Study: The bacteria and microbes in a mother’s gut can regulate fetal brain development in mice by altering gene expression, finds a new study in Nature by NYSCF – Robertson Neuroscience Investigator Elaine Hsiao, PhD, of UCLA.

The Importance: This study illuminates the importance of the gut microbiota for typical brain development in mice, a factor that may also be an important player in human brain development.

Do the millions of microscopic microbes in a mother’s gut matter for fetal brain development? Dr. Hsiao’s team aimed to find out by depleting the gut microbiota in mice – either by administering antibiotics or raising them in microbe-free environments.

“Depleting the maternal gut microbiota, using both methods, similarly disrupted fetal brain development,” the study’s lead author, Helen Vuong, PhD, a postdoctoral scholar in Dr. Hsiao’s lab, explained in a press release.

Wiping the mother mouse’s gut clean of microbes changed which genes were turned on or off in her developing offspring, ultimately disrupting formation of axons (the fibers that help brain cells communicate) in the fetal brains.

“These axons are particularly important for the ability to sense the environment,” noted Dr. Vuong. “Consistent with this, offspring from mothers lacking a gut microbiota had impairments in particular sensory behaviors.”

The researchers discovered that a mother’s gut microbiota regulates which metabolites enter a developing brain.

“When we measured the types and levels of molecules in the maternal blood, fetal blood and fetal brain, we found that particular molecules, known as metabolites, produced during the breakdown of food,  were commonly decreased or missing when the mother was lacking a gut microbiota during pregnancy,” added Dr. Vuong.

“When we grew neurons in the presence of these metabolites, they developed longer axons and greater numbers of axons,” Dr. Vuong continued. “And when we supplemented the pregnant mice with key metabolites that were decreased or missing when the microbiota was depleted, levels of those metabolites were restored in the fetal brain and the impairments in axon development and in offspring behavior were prevented.”

These results indicate that the bacteria in the gut are important for typical fetal brain development in mice, and further study will reveal whether the same is true for humans.

“We don’t know whether and how the findings may apply to humans,” said Dr. Hsiao, Associate Professor of Digestive Diseases at the David Geffen School of Medicine at UCLA. “However, there are many neurodevelopmental disorders that are believed to be caused by both genetic and environmental risk factors experienced during pregnancy. Our study suggests that maternal gut microbiota during pregnancy should also be considered and further studied as a factor that could potentially influence not only the health of the mother but the health of the developing offspring as well.”

Journal Article:

The maternal microbiome modulates fetal neurodevelopment in mice
Helen E. Vuong, Geoffrey N. Pronovost, Drake W. Williams, Elena J. L. Coley, Emily L. Siegler, Austin Qiu, Maria Kazantsev, Chantel J. Wilson, Tomiko Rendon & Elaine Y. Hsiao. 2020. Nature. DOI: https://doi.org/10.1038/s41586-020-2745-3

Photo credit: UCLA