The gut’s “second brain” may be far more involved in immune health than previously understood.
In a study published in Science, researchers at Mass General Brigham mapped how the enteric nervous system (ENS), the vast network of neurons lining the intestine, responds to bacteria, parasites and allergens. The findings reveal a complex communication system between gut nerves and immune cells that helps the digestive tract adapt to changing conditions and maintain stability.
“The enteric nervous system (ENS) is a vast network of nerves built into the walls of the intestine,” said Ramnik Xavier, M.D., Ph.D., senior author of the study and molecular biologist at Massachusetts General Hospital. “While it is well known for its role in regulating digestion and the movement of food through the intestine, researchers are learning that its influence extends much further. Our study adds to accumulating evidence showing that the ENS works closely with the immune system to help the body respond to bacteria, parasites and allergens.”
Using advanced imaging and genetic tools, the team profiled thousands of individual gut neurons in mice, examining how they behaved under different conditions, from germ-free states to allergic inflammation and parasitic infection. They found that sensory neurons changed dramatically in response to immune molecules, while motor neurons that control gut movement shifted more gradually but remained stable in number.
Together, these patterns suggest the gut’s nervous system helps the intestine fine-tune its activity, ramping up or calming down as needed to protect the body from harm.
Researchers say the work creates a foundation for studying how gut inflammation, food allergy or microbiome changes may influence the signals that connect the gut to the brain. Understanding those pathways could eventually shed light on why digestive or immune disorders can affect mood, appetite, and overall health.
This research was supported by the Leona M. and Harry B. Helmsley Charitable Trust, the Crohn’s & Colitis Foundation, Food Allergy Research & Education (FARE), the National Institutes of Health, and the Klarman Cell Observatory. The authors reported unrelated affiliations with several biomedical companies.