Gut-Brain Pathway for Appetite Loss

Researchers at University of California, San Francisco, led by David Julius and Richard Li, with key contributions from Koki Tohara, have identified the molecular pathway that connects the gut immune system to the brain during parasitic infections, explaining the phenomenon of appetite loss. The study, published in Nature, reveals an unexpected communication system between two rare cell types in the gut: tuft cells and enterochromaffin (EC) cells. Tuft cells detect parasites and release acetylcholine, a chemical messenger, which then triggers EC cells to release serotonin. This serotonin activates vagal nerve fibers, sending signals to the brain that suppress appetite. The team also discovered that tuft cells release acetylcholine in two distinct phases, explaining why appetite loss is often delayed. This breakthrough has significant implications beyond parasitic infections, potentially offering new insights and treatment strategies for conditions like irritable bowel syndrome, food intolerances, and chronic visceral pain. The work was conducted in collaboration with Stuart Brierley and his lab at University of Adelaide and received funding from entities like United States — National Institutes of Health and Howard Hughes Medical Institute.