Study Finds Gut Bacteria Generate Neurotransmitters That Shape Immune System

Researchers from Weill Cornell Medicine have found that certain bacteria establish themselves in the gut soon after birth and generate serotonin, a neurotransmitter that instructs immune cells in the gut. This process aids in the prevention of allergic reactions to both food and microbes in the early stages of development.

According to a study published in Science Immunology on March 15, it was found that bacteria found in the intestines of newborns produce serotonin. This serotonin helps in the growth of immune cells known as T-regulatory cells or Tregs. These cells play a role in preventing autoimmune diseases and allergic reactions caused by harmless food or beneficial gut microbes by suppressing inappropriate immune responses.

"The gut is now known as the second human brain as it makes over 90 per cent of the neurotransmitters in the human body. While neurotransmitters such as serotonin are best known for their roles in brain health, receptors for neurotransmitters are located throughout the human body," explained the study's senior author, Dr. Melody Zeng, 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.

The scientists noted that the gut of newborn mice contains significantly higher amounts of neurotransmitters, such as serotonin, compared to the gut of adult mice. Dr. Zeng explained that previous research on gut neurotransmitters mainly focused on adult animals and human subjects, where a particular type of gut cell called enterochromaffin cells produced neurotransmitters. However, the researchers found that this is not the case in the gut of newborn mice, where bacteria, which are more prevalent in the neonatal gut, are responsible for producing most of the serotonin.

The Zeng lab, in partnership with the Neonatal Intensive Care Unit at NewYork-Presbyterian Alexandra Cohen Hospital for Women and Newborns, has established a biobank of human infant stool samples. These samples, which were collected with the consent of the parents and made anonymous, also confirmed this finding in babies.

The findings of the study indicate that in the early stages of development, when the neonatal gut is not yet capable of producing its own neurotransmitters, specific gut bacteria might provide the necessary neurotransmitters for crucial biological processes.

"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 gut serotonin levels high," said the study's lead author Dr Katherine Sanidad, a postdoctoral associate in paediatrics at Weill Cornell Medicine.

The high serotonin levels shift 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 gut needs these serotonin-producing bacteria to keep the immune system in check," Dr. Sanidad added.

Dr. Zeng emphasized the significance of having the appropriate beneficial bacteria shortly after birth. In developed nations, babies have easier access to antibiotics, lower exposure to various microbes due to their sanitized surroundings, and potentially unhealthy diets that can greatly affect the levels of serotonin-producing bacteria in their intestines.

Consequently, these infants might possess a reduced number of Tregs and experience immune responses towards their own intestinal bacteria, leading to the development of food allergies. This could potentially explain the rising prevalence of food allergies in children, especially in developed nations. According to the expert, if infants are appropriately educated, their immune system would acknowledge that substances like peanuts and eggs are harmless, thus avoiding any attacks. Additionally, this could potentially influence the likelihood of developing autoimmune diseases in adulthood, where the immune system mistakenly targets the body's own healthy cells.

The next step for the team involves examining bacteria found in stool samples from human infants. Their objective is to assess the levels of serotonin, as well as other neurotransmitters and molecules that could potentially aid in the development of the immune system. This research aims to reduce the risk of future immune-related illnesses like allergies, infections, and cancer.

"It's essential to understand how the immune system is trained during early life, but this is understudied in newborns and children. Further studies of these developmental periods may hopefully lead us to mitigation approaches to reduce the risk of inflammatory diseases like food allergies and inflammatory bowel disease later in life," Dr Sanidad said.

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