Weill Cornell Medicine researchers discovered that unique bacteria colonize the gut soon after birth and produce the neurotransmitter serotonin to educate immune cells in the gut. This prevents allergic reactions to foods and the bacteria themselves during the early stages of development.
The preclinical study, published in Scientific immunology on March 15, showed that bacteria abundant in the intestines of newborns produce serotonin, which promotes the development of immune cells called regulatory T cells or Tregs. These cells suppress inappropriate immune responses to help prevent autoimmune diseases and dangerous allergic reactions to harmless foods or beneficial gut microbes.
“The gut is now known as the second human brain, as it produces more than 90 percent of the human body’s neurotransmitters. While neurotransmitters such as serotonin are best known for their role in brain health, neurotransmitter receptors “They are found throughout the human body,” explained the study’s lead author, Dr. Melody Zeng, assistant professor of immunology at the Gale and Ira Drukier Institute for Children’s Research and the Department of Pediatrics at Weill Cornell Medicine.
Gut bacteria in babies help
The researchers observed that the neonatal mouse intestine had much higher levels of neurotransmitters, including serotonin, than the adult intestine. “Until now, almost all studies on intestinal neurotransmitters have been conducted in adult animals or humans, where a specific type of intestinal cells called enterochromaffin cells produce neurotransmitters,” Dr. Zeng said. “However, we found that this is not the case in the newborn intestine, where most of the serotonin is produced by bacteria that are more abundant in the neonatal intestine.”
This was also confirmed in babies through a human infant stool biobank that the Zeng lab has established in collaboration with the Neonatal Intensive Care Unit at Alexandra Cohen Presbyterian Hospital for Women and Newborns in New York. These samples were obtained with parental consent and were anonymized.
The study results suggest that before the neonatal intestine is mature enough to produce its own neurotransmitters, unique intestinal bacteria can supply neurotransmitters that are necessary for critical biological functions during early development.
“We found that gut bacteria in young mice not only directly produce serotonin but also decrease an enzyme called monoamine oxidase that normally breaks down serotonin, thus keeping serotonin levels high in the gut,” said the study’s lead author, Dr. Katherine Sanidad, postdoctoral associate in pediatrics. in Weill Cornell Medicine.
High levels of serotonin change the balance of immune cells by increasing the number of Tregs, which helps prevent the immune system from overreacting and attacking gut bacteria or food antigens. “The neonatal intestine needs these serotonin-producing bacteria to keep the immune system under control,” added Dr. Sanidad.
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 soon after birth. Babies in developed countries have better access to antibiotics, less exposure to various microbes in their clean environments, and potentially unhealthy diets that can significantly affect the abundance of serotonin-producing bacteria in their intestines.
As a result, these babies may have fewer Tregs and develop immune reactions to their own gut bacteria or food allergies. This may be one of the reasons why food allergies have become increasingly common in children, especially in developed countries. “If raised properly, babies’ immune systems would recognize that things like peanuts and eggs are okay, and it doesn’t have to attack them,” she said. This can also have an impact on the development of autoimmune diseases (when the immune system attacks the body’s own healthy cells) later in life.
Next, the team plans to look at bacteria in stool samples from human babies to measure their production of serotonin, other neurotransmitters, and molecules that can help train the immune system to prevent future immune-related diseases, such as allergies, infections, and cancer. .
“It is essential to understand how the immune system is trained during the early stages of life, but this is understudied in newborns and children. Hopefully, further studies of these developmental periods will lead us to mitigation approaches to reduce the risk.” risk of inflammatory diseases such as food allergies and intestinal inflammation. disease later in life,” said Dr. Sanidad.
Dr. Melody Zeng’s laboratory is supported in part by grants from the National Institutes of Health. R01HD110118, R01HL169989, R21CA270998 and K01DK114376; The Starr Cancer Consortium; the Hartwell Foundation; and the Jill Roberts Center for Inflammatory Bowel Disease, the Council on Children’s Health, and the Drukier Institute for Children’s Health at Weill Cornell Medicine.