Study Finds Microbes Shape Brain Development Before and After Birth

Microbes are present throughout our environment and influence crucial bodily functions. New research from Michigan State University has demonstrated that microbes also contribute to shaping the developing brain, particularly in an area critical for regulating stress, social behavior, and essential physiological processes.

The study, published in Hormones and Behavior, used a mouse model to investigate how natural microbial exposure affects brain development both immediately after birth and potentially during gestation. Mice were chosen because they share important biological and behavioral traits with humans and are the only viable model for exploring microbial influences on brain development.

This work gains relevance in light of modern obstetric practices, such as peripartum antibiotic use and Cesarean delivery, which alter the microbiomes of mothers and newborns. In the United States, about 40% of women receive antibiotics around childbirth, and nearly one-third of all births are via Cesarean section. “At birth, a newborn body is colonized by microbes as it travels through the birth canal. Birth also coincides with important developmental events that shape the brain. We wanted to further explore how the arrival of these microbes may affect brain development,” said Alexandra Castillo Ruiz, lead author of the study.

The research focused on the paraventricular nucleus of the hypothalamus (PVN), a brain region involved in regulating stress, blood pressure, water balance, and social behavior. Previous work by the team showed that germ-free mice—those raised without microbes—had increased neuronal death in the PVN during early development. This study aimed to determine whether fewer neurons persisted into adulthood and whether these effects stemmed from microbial colonization after birth or signals from maternal microbes during pregnancy. 

To explore this, the researchers used cross-fostering: germ-free newborn mice were placed with mothers that had microbes and compared to control groups. Brain analysis at three days old revealed that all mice gestated by germ-free mothers had fewer PVN neurons, regardless of microbial exposure after birth. In adulthood, germ-free mice also had fewer PVN neurons.

“Our study shows that microbes play an important role in sculpting a brain region that is paramount for body functions and social behavior. In addition, our study indicates that microbial effects start in the womb via signaling from maternal microbes,” said Dr. Castillo-Ruiz. She added, “Rather than shunning our microbes, we should recognize them as partners in early life development. They’re helping build our brains from the very beginning.”