Summary: New research highlights the critical role of unique gut bacteria in newborns, producing serotonin to educate immune cells and prevent allergic reactions early in life.
The study reveals that these bacteria encourage the development of T-regulatory cells, crucial for suppressing inappropriate immune responses and preventing autoimmune diseases. This work suggests that before the neonatal gut matures to produce its own neurotransmitters, specific bacteria supply essential serotonin, promoting a balanced immune system.
Such findings underscore the importance of early exposure to beneficial bacteria for preventing allergies and potentially autoimmune diseases later in life.
Key Facts:
- Serotonin-Producing Gut Bacteria: Newly born infants’ guts harbor special bacteria that produce serotonin, crucial for developing a healthy immune system by fostering T-regulatory cells.
- Prevention of Allergies: This mechanism helps in preventing dangerous allergic reactions to food and beneficial microbes by maintaining a high level of serotonin, which keeps the immune response in check.
- Critical Early Development Role: The research emphasizes the significance of the right microbial exposure after birth, suggesting a potential link between reduced diversity in gut bacteria due to modern lifestyles and the rise in food allergies among children in developed countries.
Source: Weill Cornell University
Weill Cornell Medicine investigators discovered that unique bacteria colonize the gut shortly after birth and make the neurotransmitter serotonin to educate gut immune cells. This prevents allergic reactions to food and the bacteria themselves during early development.
The preclinical study, published in Science Immunology on Mar. 15, showed that bacteria abundant in the guts 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 harmless food items or beneficial gut microbes.
“The gut is now known as the second human brain as it makes over 90 percent 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.
Gut Bacteria in Babies Provide a Helping Hand
The researchers observed that the neonatal mouse gut had much higher levels of neurotransmitters, including serotonin, than the adult gut.
“So far, almost all studies of gut neurotransmitters were conducted in adult animals or human subjects, where a specific gut cell type called enterochromaffin cells produce neurotransmitters,” said Dr. Zeng.
“However, we discovered that this isn’t the case in the newborn gut where most of the serotonin is made by bacteria that are more abundant in the neonatal gut.”
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 in the NewYork-Presbyterian Alexandra Cohen Hospital for Women and Newborns. These samples were obtained with parental consent and deidentified.
The study results suggest that before the neonatal gut is mature enough to make its own neurotransmitters, unique gut bacteria may supply neurotransmitters that are needed 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 gut serotonin levels high,” said the study’s lead author Dr. Katherine Sanidad, postdoctoral associate in pediatrics 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.
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 diverse microbes in their clean environments and potentially unhealthy diets that may significantly impact 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 allergies to food. This may be one reason food allergies have become increasingly common in children, particularly in developed countries.
“If educated properly, the immune system in babies would recognize that things like peanuts and eggs are okay, and it doesn’t have to attack them,” she said. This may also have an impact on developing autoimmune diseases—when the immune system attacks the body’s own healthy cells—later in life.
The team next plans to look at bacteria in human infant stool samples to measure their production of serotonin, other neurotransmitters and molecules that may help train the immune system to prevent future immune-related diseases, such as 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.
Funding: Dr. Melody Zeng’s lab is supported in part by the National Institutes of Health grants R01HD110118, R01HL169989, R21CA270998, and K01DK114376; The Starr Cancer Consortium; the Hartwell Foundation; and the Jill Roberts Center for Inflammatory Bowel Disease, the Children’s Health Council, and the Drukier Institute for Children’s Health at Weill Cornell Medicine.
About this microbiome research news
Author: Krystle Lopez
Source: Weill Cornell University
Contact: Krystle Lopez – Weill Cornell Univerity
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Gut bacteria-derived serotonin promotes immune tolerance in early life” by Melody Zeng et al. Science Immunology
Abstract
Gut bacteria-derived serotonin promotes immune tolerance in early life
The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remain largely undefined.
Here, we demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin, and that specific gut bacteria directly produce serotonin while down-regulating monoamine oxidase A to limit serotonin breakdown.
We found that serotonin directly signals to T cells to increase intracellular indole-3-acetaldehdye and inhibit mTOR activation, thereby promoting the differentiation of regulatory T cells, both ex vivo and in vivo in the neonatal intestine.
Oral gavage of serotonin into neonatal mice resulted in long-term T cell–mediated antigen-specific immune tolerance toward both dietary antigens and commensal bacteria.
Together, our study has uncovered an important role for specific gut bacteria to increase serotonin availability in the neonatal gut and identified a function of gut serotonin in shaping T cell response to dietary antigens and commensal bacteria to promote immune tolerance in early life.
