When a stomach bug hits hard, you often stop wanting to eat, even after the worst symptoms fade. The same thing happens to millions of people who carry long‑lasting worm infections. Scientists have now uncovered why the appetite disappears.
Researchers at the University of California, San Francisco found a direct link between the gut’s immune response and the brain during a worm infection. Their study, released in Nature on March 25, shows how gut cells talk to the brain and make you feel less hungry.
How Gut Cells Talk to the Brain
The team focused on two special gut cells. Tuft cells act like detectors that sense parasites and start the immune defense. Enterochromaffin (EC) cells release chemicals that trigger nerves connected to the brain. EC cells are already known to cause nausea, pain, and gut discomfort, but it was unclear whether they speak directly with tuft cells.
In lab experiments, adding acetylcholine (a messenger chemical) to gut tissue caused EC cells to release serotonin. The serotonin then activated the vagus nerve, which carries messages from the gut to the brain.
"Tuft cells use acetylcholine like neurons do, but with a completely different tool kit," said lead researcher Tohara. "They can send signals without the usual neuron machinery."
A Two‑Step Signal That Delays Appetite Loss
The scientists discovered that tuft cells release acetylcholine in two phases. First, they send a quick burst of the chemical. As the infection grows and more tuft cells appear, they begin a slower, steady release. This long‑lasting signal is strong enough to trigger EC cells and, ultimately, the brain.
What This Means for Gut Disorders
To see if the pathway works in real animals, the team infected mice with parasitic worms. Normal mice ate less as the infection progressed. Mice whose tuft cells could not make acetylcholine kept eating normally. This proved that the tuft‑EC‑brain signal directly drives appetite changes.
These results could help create new treatments for symptoms linked to worm infections and other gut problems. "If we can control what tuft cells release, we might be able to manage several physiological responses," said Locksley.
Tuft cells are also found in the airways, gallbladder, and reproductive system. Problems with this signaling route may play a role in irritable bowel syndrome, food intolerances, and chronic abdominal pain.
The research was done together with Stuart Brierly, PhD, and his team at the University of Adelaide, Australia.