What is already known
The gut is known to produce most of the human body’s neurotransmitters — signaling molecules that influence the function of neurons. Previous studies have linked the neurotransmitter serotonin to the movement of food in the gastrointestinal system as well as to flare-ups of inflammatory bowel diseases. But the relationship between serotonin and immune cells in the gut remains mysterious.
What this research adds
Working in mice, researchers found that newborns have higher levels of serotonin and serotonin-producing bacteria in their guts compared to adults. In newborns, gut bacteria not only produce serotonin but also inhibit an enzyme responsible for its breakdown, maintaining high serotonin levels in the gut. There, serotonin stimulates the production of regulatory T cells, a type of immune cells that dampen immune responses and promote tolerance to harmless food and bacteria.
Conclusions
The findings suggest that the infant microbiota produces neurotransmitters that are required for the development of the immune system.
During early life, gut microbes play an important role in building a robust immune system, which can help prevent allergies later in life. Now, researchers have found that the infant gut microbiota produces the neurotransmitter serotonin to promote immune tolerance.
The findings, published in Science Immunology, suggest that the infant microbiota provides important neurotransmitters that shape the immune system.
“The gut is now known as the second human brain as it makes over 90 percent of the neurotransmitters in the human body,” says study senior author Melody Zeng at Weill Cornell Medicine in New York. “While neurotransmitters such as serotonin are best known for their roles in brain health, receptors for neurotransmitters are located throughout the human body.”
Previous studies have linked serotonin to the movement of food in the gastrointestinal system as well as to flare-ups of inflammatory bowel diseases. To investigate the relationship between serotonin and immune cells in the gut, Zeng and her team studied the neurotransmitters produced in the gut of newborn mice.
Serotonin-producing microbes
The researchers found that the gut of newborn mice had higher levels of serotonin and other neurotransmitters than the gut of adult mice. The newborn’s gut also had higher levels of serotonin-producing bacteria. Lactobacillus species, including Lactobacillus murinus, made up more than 90% of bacteria in the pups’ guts.
The same pattern was observed in stool from babies. Of 26 bacterial species found in infant stool samples, 16 produced the neurotransmitter serotonin. These bacterial species include Staphylococcus aureus, Clostridium perfringens, Klebsiella grimontii, Staphylococcus epidermis and Enterobacter cloacae. Smaller proportions of serotonin-producing bacteria were found in bacterial isolates from adult human stool.
“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,” Zeng says. “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.”
Regulating immune responses
Next, the team found that gut bacteria in newborn mice not only produce serotonin, they also decrease an enzyme that breaks it down. This likely helps to keep high levels of serotonin in the gut.
Further experiments showed that serotonin stimulates the differentiation of regulatory T cells, a type of immune cells that dampen immune responses and promote tolerance to harmless food and bacteria. “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,” Zeng says.
In the future, the researchers plan to look at serotonin and other neurotransmitters produced in the gut of newborn babies. Investigating the relationship between neurotransmitters and gut immune cells in early life, Zeng says, “may hopefully lead us to mitigation approaches to reduce the risk of inflammatory diseases like food allergies and inflammatory bowel disease later in life.”
