Intestinal Bacteria Produce Neurotransmitters that Influence the Baby's Immune System

Researchers at Weill Cornell Medicine discovered that unique bacteria colonize the gut shortly after birth and produce the neurotransmitter serotonin to train the gut’s immune cells. This prevents allergic reactions to food and the bacteria themselves during early development. The preclinical study, published in Science Immunology, shows that bacteria abundant in the gut of newborns produce serotonin, which promotes the development of immune cells called T-regulatory cells or Tregs. These cells suppress inappropriate immune responses, helping to prevent autoimmune diseases and dangerous allergic reactions to harmless foods or beneficial gut microbes.

The Gut of Newborns Needs Serotonin

The gut is now considered the second human brain, as it produces over 90 percent of the neurotransmitters in the human body. While neurotransmitters such as serotonin are best known for their role in brain health, receptors for neurotransmitters are found throughout the human body. This was explained by the study’s lead author, Dr. Melody Zeng, an assistant professor of immunology at the Gale and Ira Drukier Institute for Children’s Research and the Department of Pediatrics at Weill Cornell Medicine.

The researchers observed that the gut of newborn mice contained many more neurotransmitters, including serotonin, than the gut of adults. So far, almost all studies on neurotransmitters in the gut have been conducted in adult animals or humans, where a specific cell type of the gut, the enterochromaffin cells, produce neurotransmitters, Zeng explained. The researchers have found that this is not the case in the gut of newborns, as most serotonin is produced by bacteria, which are found in greater numbers in the gut of newborns.

This was also confirmed in infants by a human stool biobank that the Zeng lab established in collaboration with the neonatal intensive care unit at NewYork-Presbyterian Alexandra Cohen Hospital for Women and Newborns. These samples were collected with parental consent and anonymized. The study results suggest that unique gut bacteria may provide neurotransmitters needed for important biological functions during early development, before the newborn’s gut is mature enough to produce its own neurotransmitters.

The researchers found that gut bacteria in young mice not only produce serotonin directly, but also reduce an enzyme called monoamine oxidase that normally breaks down serotonin, keeping gut serotonin levels high. The high levels of serotonin shift the balance of immune cells by increasing the number of Tregs, which prevents the immune system from overreacting and attacking gut bacteria or food antigens. Newborns’ guts need these serotonin-producing bacteria to keep the immune system in check.

The Immune System is Trained in the First Years of Life

Dr. Zeng noted that this work underscores the importance of having the right types of beneficial bacteria soon after birth. Babies in developed countries have better access to antibiotics, are less exposed to different microbes in their clean environments, and may eat unhealthy diets, which can significantly affect the abundance of serotonin-producing bacteria in their gut.

As a result, these babies may have fewer Tregs and develop immune reactions to their own gut bacteria or allergies to foods. This could be one reason why food allergies are becoming more common in children, especially in developed countries. When raised correctly, babies’ immune systems recognize that things like peanuts and eggs are okay and it doesn’t need to attack them. This could also impact the development of autoimmune diseases, in which the immune system attacks the body’s own healthy cells, later in life.

Next, the team plans to examine bacteria in stool samples from human infants to measure their production of serotonin, other neurotransmitters and molecules that can train the immune system to prevent future immune-related diseases such as allergies, infections and cancer. It is important to understand how the immune system is trained in the first years of life, but this has not yet been sufficiently researched in newborns and children. Further study of these developmental phases could hopefully lead us to approaches that reduce the risk of inflammatory diseases such as food allergies and inflammatory bowel disease later in life.