Tiny Microbes Could Secretly Rewire the Brain Before Birth

New research from Michigan State University shows that microbes play an important role in early brain development, particularly in a key region of the brain that controls stress, social behavior, and vital bodily functions. The study, published in Hormones and Behavior, used a mouse model to show that natural microbes not only affect brain structure immediately after birth, but can even influence development in the womb. A mouse model was chosen because mice share significant biological and behavioral similarities with humans, and there are no other alternatives for studying the role of microbes in brain development.

The Influence of Microbes on the Infant Brain

This work is significant because modern obstetric practices such as the use of antibiotics during birth and cesarean deliveries disrupt maternal microbes. In the United States alone, 40% of women receive antibiotics around the time of birth, and one-third of all births are by cesarean section. “During birth, a newborn’s body is colonized by microbes as it passes through the birth canal. Birth also coincides with important developmental events that shape the brain. We wanted to further investigate how the arrival of these microbes might influence brain development,” said Alexandra Castillo Ruiz, lead author of the study and assistant professor at the MSU Department of Psychology.

The research team focused on a brain region called the paraventricular nucleus of the hypothalamus (PVN), which plays a central role in regulating stress, blood pressure, water balance, and even social behavior. Their previous work had shown that mice raised without microbes, i.e., germ-free mice, had more dying neurons in the PVN during their early development. The new study aimed to clarify whether this increased cell death led to long-term changes in neuron numbers and whether these effects were caused by the arrival of microbes at birth or were triggered in the womb by signals from the mother’s microbes.

Partners in Early Life Development

To find out, the researchers used a cross-fostering approach. Germ-free newborn mice were placed with mothers with microbes and compared with control groups. When the brains of these mice were examined just three days after birth, the results were striking: All mice born to germ-free mothers had fewer neurons in the PVN, regardless of whether they received microbes after birth. They also found that germ-free adult mice had fewer neurons in the PVN. “Our study shows that microbes play an important role in the development of a brain region that is critical for bodily functions and social behavior. Furthermore, our study suggests that microbial influences begin in utero through signals from maternal microbes,“ said Dr. Castillo-Ruiz. ”Instead of avoiding our microbes, we should recognize them as partners in early life development,“ said Dr. Castillo-Ruiz. ”They help build our brains from the very beginning.”