Scientists have discovered a biological appetite suppression mechanism through which the human body, in response to a pathological process, transmits a signal to the central nervous system to reduce food intake.
According to the latest research, specialized cells in the intestinal epithelium identify pathogens and send neurochemical impulses that trigger this appetite suppression mechanism in the brain. This process is dynamic and develops over time, which explains the clinical phenomenon of why a patient feels relatively stable at the initial stage of an infection, while their appetite diminishes as the disease progresses.
What Does the Study Say?
For any patient who has experienced a severe gastrointestinal infection, this clinical picture is well known: even after partial remission of symptoms, the appetite does not return for a long time. Similar symptoms are observed in millions of patients suffering from chronic helminthiasis (parasitic worm infection). Despite the wide prevalence of this pathology, scientists were long unable to explain the exact cause of this phenomenon.
In March of this year, the journal Nature published a new study by scientists from the University of California, San Francisco (UCSF), which describes a previously unknown form of intercellular communication that may play a fundamental role in the management of gastroenterological pathologies.
“Our scientific interest was not only to determine the mechanisms of the immune response but also to discover how the immune system recruits the peripheral nervous system to modify behavior,” said study co-author David Julius, winner of the 2021 Nobel Prize in Physiology or Medicine.
How Do Gut Cells signal appetite loss to the Brain?
The study focused on two rare cell types in the intestinal epithelium: tuft cells, which act as detectors by identifying pathogens and initiating immune defense, and enterochromaffin (EC) cells, which release chemical signals and stimulate neural pathways connected to the brain. It was already known that EC cells cause feelings of nausea, pain, and discomfort; however, it was previously unknown whether they interacted directly with tuft cells.
To investigate this, scientists placed genetically modified sensory cells next to tuft cells under a microscope. When the tuft cells were exposed to succinate—a compound secreted by parasitic worms—the neighboring sensory cells lit up. The process revealed that tuft cells were secreting acetylcholine, a signaling molecule typically associated with nerve cells.
When acetylcholine reached laboratory-grown intestinal tissue containing enterochromaffin cells, the cells responded by releasing serotonin, which in turn activated the vagus nerve fibers that carry signals from the gut to the brain.
Delayed Signaling: The Scientific Explanation for Loss of Appetite
The study also revealed that tuft cells release acetylcholine in two stages—a fact that explains why appetite disappears gradually as the disease progresses. At the beginning of an infection, tuft cells emit short, rapid signals. Then, as the immune response grows, the number of these cells increases and they send slow, steady signals—strong enough to activate the enterochromaffin cells and deliver the message to the brain.
“The gut effectively waits until it is sure the threat is real and persistent—and only then calls on the brain to change behavior,” Julius explains.
Future Perspectives of the Research
To confirm the behavioral effects of this signaling pathway in vivo (in a living organism), the research team studied a population of mice infected with helminthiasis. In mice with normal tuft cell function, food intake significantly decreased as the infection progressed. In contrast, mice whose tuft cells lacked the ability to synthesize acetylcholine continued to eat at a standard rate. This experiment confirmed that the identified signaling pathway directly regulates changes in appetite.
These findings may help scientists develop new methods for treating symptoms associated with parasitic infections in the future. It is also noteworthy that tuft cells are localized in various parts of the body, including the respiratory tract, gallbladder, and reproductive system, and not just in the gut.
Consequently, controlling the secretory function of tuft cells may provide an effective means for managing physiological reactions associated with Irritable Bowel Syndrome (IBS), food intolerance, and chronic visceral pain.
The study was conducted by UCSF in close collaboration with the University of Adelaide (Australia).
Source: Sciencedaily.com
