Can gut bacteria help shape newborn's immune system? Study sheds light

Researchers from Weill Cornell Medicine have discovered that unique bacteria colonize the gut shortly after birth and make the neurotransmitter serotonin to educate gut immune cells that help in preventing allergic reactions to food and the bacteria themselves during early development.

The study published in the journal Science Immunology on March 15, 2024, revealed 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.

For the study, researchers analyzed neonatal mouse gut and observed that they 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."

The study results suggested 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.

Reference:Katherine Z. Sanidad, Stephanie L. Rager, Hannah C. Carrow, Aparna Ananthanarayanan, Ryann Callaghan, Lucy R. Hart, Tingting Li, Purnima Ravisankar, Julia A. Brown, Mohammed Amir, Jenny C. Jin, Alexandria Rose Savage, Ryan Luo, Florencia MardorskyRowdo, M. Laura Martin, Randi B. Silver, Chun-Jun Guo, Jan Krumsiek, Naohiro Inohara, Melody Y. Zeng. Gut bacteria–derived serotonin promotes immune tolerance in early life. Science Immunology, 2024; 9 (93) DOI: 10.1126/sciimmunol.adj4775