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Preclinical studies published March 15 in Science Immunology show that a large number of bacteria 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 to help prevent autoimmune diseases and dangerous allergic reactions to harmful food items or beneficial gut microbes.
“The gut is now known as the second human brain because it produces more than 90 percent of the neurotransmitters in the human body. Although neurotransmitters such as serotonin are best known for their role in brain health, receptors for neurotransmitters are located throughout the human body,” explained the study’s senior author, Dr. Melody Zheng is an assistant professor of immunology in the Gale and Ira Drukier Institute for Children’s Research and the Department of Pediatrics at Weill Cornell Medicine.
Gut bacteria in children lend a helping hand
The researchers found that the guts of newborn mice had much higher levels of neurotransmitters, including serotonin, than the guts of adults. “Until now, almost all research on gut neurotransmitters has been conducted in adult animals or humans, where a specific gut cell called enterochromaffin cells produces neurotransmitters,” said Dr. Zeng. “However, we discovered that this is not the case in the neonatal gut where most of the serotonin is produced by bacteria that are abundant in the neonatal gut.”
This has also been confirmed in children through a human infant stool biobank that the Zeng lab established in collaboration with the Neonatal Intensive Care Unit for Women and Newborns at NewYork-Presbyterian Alexandra Cohen Hospital. These samples were obtained with parental consent and were de-identified.
The study results suggest that before the newborn gut is mature enough to produce its neurotransmitters, unique gut bacteria may provide the neurotransmitters needed for important biological functions during early development.
“We found that gut bacteria in young mice not only produced serotonin directly but also reduced an enzyme called monoamine oxidase that normally breaks down serotonin, thus keeping gut serotonin levels high,” said study lead author Dr. Catherine Sanidad, a pediatrics postdoctoral associate. in Weill Cornell Medicine.
High serotonin levels alter the balance of immune cells by increasing the number of Tregs, which help prevent the immune system from overreacting and attacking gut bacteria or food antigens. “These serotonin-producing bacteria in the neonate’s gut are needed to keep the immune system in check,” Dr. Sanidad added.
A healthy immune system helps later in life
Dr. Zeng noted that this work underscores the importance of having the right types of beneficial bacteria right after birth. Children in developed countries have better access to antibiotics, less exposure to various microbes in their clean environment, and potentially unhealthy diets that can significantly affect the abundance of serotonin-producing bacteria in their gut.
As a result, these children may have fewer Tregs and develop immunity to their own gut bacteria, or food allergies. This may be one reason food allergies have become increasingly common in children, especially in developed countries. “If properly educated, the immune system in children is okay with things like peanuts and eggs and it doesn’t have to attack them,” she said. It can also affect the development of autoimmune diseases–when the immune system attacks the body’s own healthy cells–later in life.
The team next plans to look at the bacteria in human baby stool samples to measure their production of serotonin, other neurotransmitters and molecules that could help train the immune system to fight future immune-related diseases such as allergies, infections and cancer.
“Understanding how the immune system is trained early in life is essential, but is understudied in infants and children. Further study of this developmental period can hopefully lead us to mitigation strategies to reduce the risk of inflammatory diseases such as food allergies and inflammatory bowel disease. . Diseases later in life, ” said Dr. Sanidad.
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