Researchers Identify Mechanism Behind Appetite Loss When You Are Sick - Video

A groundbreaking study from the University of California, San Francisco, published in Nature, reveals how the gut communicates with the brain to suppress appetite during infection. The findings uncover a precise biological pathway explaining why appetite loss often appears later in illness rather than immediately.

Researchers discovered that the process begins with specialized gut cells called tuft cells, which act as immune sentinels. These cells detect parasitic infections by sensing compounds such as succinate released by worms. Once activated, tuft cells release acetylcholine, a signaling molecule typically associated with nerve cells. This was a surprising finding, as tuft cells are not neurons but can mimic their communication style.

The signal is then picked up by neighboring enterochromaffin cells, which respond by releasing serotonin. This chemical activates the vagus nerve, a key communication pathway between the gut and the brain. Through this gut–brain axis, the brain receives signals that reduce appetite and alter behavior during infection.

A key insight from the study is the two փուլ signaling pattern. Initially, tuft cells release a brief burst of acetylcholine. As the immune response intensifies and tuft cell numbers increase, they shift to a prolonged, sustained release. This delayed, but stronger signal, explains why appetite suppression often develops after the infection has taken hold rather than at its onset.

Animal experiments confirmed the mechanism. Mice with normal tuft cell function ate less during infection, while those unable to produce acetylcholine continued eating normally. This demonstrates that the pathway directly drives appetite loss.

Beyond infections, the discovery may have broader clinical implications. Disruptions in this signaling system could contribute to gastrointestinal disorders such as irritable bowel syndrome and food intolerances.

Overall, the study provides a clearer understanding of how immune responses influence behavior through the nervous system, opening new possibilities for targeted treatments that could regulate appetite and gut-related symptoms.

REFERENCE: Kouki K. Touhara, Jinhao Xu, Joel Castro, Hong-Erh Liang, Guochuan Li, Mariana Brizuela, Andrea M. Harrington, Sonia Garcia-Caraballo, Tracey O’Donnell, Daniel Neumann, Nathan D. Rossen, Fei Deng, Gudrun Schober, Yulong Li, Richard M. Locksley, Stuart M. Brierley, David Julius. Parasites trigger epithelial cell crosstalk to drive gut–brain signalling. Nature, 2026; DOI: 10.1038/s41586-026-10281-5