How the immune system switches off appetite: new research reveals a link between the gut and the brain after a parasitic infection
Loss of appetite is one of the symptoms that many people experience during an intestinal infection, and it often persists even after the most pronounced symptoms subside. This pattern is not limited only to temporary viral illnesses or food poisoning. In longer-lasting infections with parasitic worms, which still affect a large number of people in poorer parts of the world, reduced desire for food can become part of a broader health problem, associated with malnutrition, fatigue, and weakening of the body. New research by scientists from the University of California, San Francisco shows that this response is not merely a vague consequence of illness, but part of a precisely organized communication between the immune system in the gut and the nervous system.
The study, published on March 25 in the journal Nature, describes the molecular sequence by which the signal of the presence of parasites is transmitted from the intestinal mucosa to the brain, after which the body's behavior changes, including food intake. According to the research team, this is a mechanism that has so far not been sufficiently clarified, by which the body first assesses the seriousness and duration of the threat, and only then activates broader physiological responses such as nausea, discomfort, and loss of appetite. The broader message of the work is also important for science: symptoms that we usually observe as a side effect of disease may be very precisely regulated biological programs, and not a chaotic consequence of inflammation.
Two rare cell types at the center of the story
At the center of the discovery are two rare populations of cells located in the intestines. The first are the so-called tuft cells, specialized epithelial cells that recognize certain chemical traces from intestinal contents and help trigger defense against parasites. The second are enterochromaffin cells, known for releasing serotonin and participating in the generation of nausea, discomfort, changes in intestinal motility, and the transmission of signals to nerve fibers. Although it was previously known that both groups have an important role in intestinal physiology, it was not clear whether there is a direct link between them and, if so, how that link is translated into a change in behavior.
According to the UCSF team's explanation, tuft cells act as highly sensitive chemical “guards.” In this work, the scientists studied their response to succinate, a molecule produced by parasitic worms. When tuft cells are exposed to that signal, they do not trigger only a local immune response, but also release acetylcholine, a chemical messenger classically associated with nerve cells. This is where the key twist of the study appears: tuft cells are not neurons, but they use the same signaling molecule to transmit a message to other cells in the intestines.
Acetylcholine as a danger message, serotonin as a signal amplifier
The researchers showed that the acetylcholine released by tuft cells acts on enterochromaffin cells. They then release serotonin, and serotonin activates fibers of the vagus nerve, one of the main communication pathways between the gut and the brain. In other words, the gut does not send the brain a nonspecific piece of information that “something is wrong,” but a highly organized signaling package that arises in several steps: parasite detection, activation of tuft cells, release of acetylcholine, activation of enterochromaffin cells, release of serotonin, and transmission of information to the central nervous system.
This is important because it explains why loss of appetite does not have to occur immediately. According to the data from the study, tuft cells release acetylcholine in two phases. The first phase is short and transient, a kind of early alarm. The second comes later, after the immune response has fully ramped up, when the number of tuft cells increases and when they produce a slower but longer-lasting signal. It is precisely this second wave, the authors state, that may explain why a person at the beginning of the infection can still feel relatively well, and only a few days later begins to feel more pronounced nausea and a drop in appetite.
Such a two-stage organization of the response indicates that the body is trying to avoid an excessive reaction to transient or harmless stimuli. Instead of immediately changing behavior at every suspicious signal, the organism, according to the authors' interpretation, first “checks” whether the threat is real and persistent. Only when it is confirmed that the infection is ongoing and that the defense system must move to a higher level of readiness does the signal to the brain also turn on, affecting food intake and the general condition.
Experiments in mice answered the key question
To show that this was not just a laboratory curiosity at the cellular level, the scientists monitored how much food mice consumed during infection with parasitic worms. The result was clear: animals with normally functional tuft cells began to eat less as the infection progressed. By contrast, mice whose tuft cells could not produce acetylcholine did not show the same drop in appetite, even though they were exposed to infection. This confirmed that the observed molecular chain is not merely an accompanying phenomenon, but an actual driver of the change in behavior.
At the same time, the authors were cautious in interpreting the scope of their findings. The study was conducted in a mouse model and focused on one type of parasitic infection, so it cannot automatically be concluded that an identical mechanism occurs to the same extent in all people and in all diseases of the digestive system. Still, the fact that the key cells and signaling molecules have long already been known in human biology as well gives this work considerable translational weight. It does not offer a ready-made cure, but it provides a roadmap for understanding symptoms that until now have mainly been described using general formulas about the “body's response to infection.”
Why this matters beyond parasitology
Although the immediate trigger for the research is parasitic infection, the implications could be much broader. Enterochromaffin cells are already known as an important source of serotonin in the intestines and are often mentioned in research on nausea, visceral pain, and motility disorders. Tuft cells, on the other hand, have become increasingly interesting to scientists in recent years because they do not behave only as a passive part of the intestinal mucosa, but as active sensors that can translate chemical stimuli from the environment into an immune and nervous response. The new study connects these two fields and shows that part of intestinal discomfort may develop through a very specific epithelial-neural circuit.
That is precisely why the authors believe that disorders in this communication could also be relevant to conditions such as irritable bowel syndrome, food intolerances, or chronic visceral pain. This, of course, does not mean that the cause of these disorders has now been found. Such a claim would be premature. But it does mean that there is a new, biologically convincing candidate to explain at least part of the symptoms that significantly impair the quality of life of many patients, while often being difficult to objectively measure with standard diagnostic tests.
Broader context: parasitic infections are still a global public health problem
The significance of the work grows further when the global burden of disease caused by intestinal helminths is taken into account. According to the World Health Organization, infections with soil-transmitted helminths are still among the most common infections in the world. WHO estimates that around 1.5 billion people, or approximately 24 percent of the world's population, are infected with them, primarily in areas with poor access to clean water, sanitation, and hygiene. Children, adolescent girls, and pregnant and breastfeeding women in endemic areas are particularly affected, and the consequences include malnutrition, poorer physical development, anemia, and reduced work capacity.
WHO also states that certain intestinal helminths can cause loss of appetite, which then further reduces nutritional intake and worsens physical condition. In that light, the new research from San Francisco is interesting not only as an elegant molecular explanation of one symptom, but also as a potentially important step toward understanding why these infections can so strongly undermine the nutritional status of those affected. If, in the future, it turns out that some of the symptoms can be specifically alleviated without impairing the body's defensive response, this would open the way for therapies aimed not only at removing the parasites, but also at preserving the patient's functional condition during illness.
From classical immunology to the biology of behavior
One of the most interesting messages of the work is that the boundary between immunology, neuroscience, and the biology of behavior is becoming less and less rigid. Traditionally, the immune system was viewed as a network that recognizes pathogens and organizes their removal, while behavioral changes, such as reduced food intake or withdrawal from activity, were often described as general signs of illness. It is now becoming clear that these patterns are deeply rooted in specific cellular and chemical pathways. Put simply, the organism does not “lose its appetite” by chance. It reduces it through a precisely tuned system that connects peripheral sensors in the gut, local immune responses, and neural circuits that shape behavior.
Such an understanding also changes the way symptoms can be thought about. Instead of being treated exclusively as unpleasant side effects that should be suppressed at any cost, the question arises of when they are a useful part of defense and when they cross the line and become harmful. Loss of appetite during infection may in the short term be part of an adaptive response, but if it is prolonged, it can worsen the general condition, especially in children, older people, and chronically ill patients. That is precisely why mechanistic studies such as this one have value that goes beyond basic science.
Caution before transfer to clinical practice
Despite the great interest that the results will likely provoke, transfer into medical practice will not be quick. To begin with, it is necessary to confirm to what extent the same pathway is preserved in the human body and in exactly which conditions it is activated. Then it must be clarified whether blocking it would reduce symptoms without unwanted consequences for the defense against infection itself. The gut-brain axis is an exceptionally complex system, and serotonin, acetylcholine, and the vagus nerve participate in numerous physiological processes. Intervention at one point could help control nausea or loss of appetite, but at the same time cause unforeseen consequences elsewhere.
Still, the study provides a strong foundation for further research. The very fact that tuft cells use acetylcholine in a way that does not fit the classical neuronal model opens a new field of questions about how epithelial cells communicate with the rest of the organism. Additional weight is given to the work by the broader trend in contemporary biology, in which it is increasingly being shown that the intestines are not merely a place of digestion, but a complex sensory and signaling interface between the external environment and the brain.
What the new discovery says about the everyday experience of illness
For laypeople, but also for clinicians, the most concrete value of results like these may be that they explain the everyday experience of illness in a more precise way. That familiar feeling when, during an intestinal infection, food suddenly becomes “disgusting,” when appetite disappears only after a few days, or when discomfort lasts even after the worst symptoms pass, no longer seems like an elusive consequence of “a weak body.” According to the available data, this is a coordinated response in which intestinal cells sense a threat, the immune system assesses its duration, and the nervous system then adjusts the body's behavior.
It is precisely this connection between a local event in the gut and a behavioral change at the level of the whole organism that makes the research especially important. It does not offer a sensationalist reversal, but carefully clarifies one link in the complex chain connecting infection, inflammation, the sensation of discomfort, and reduced food intake. For science, this is valuable because it provides a new target for research. For medicine, it may be important because it opens the possibility of more precise symptom relief. And for the public, perhaps the most interesting thing is that it once again confirms how deeply the gut and the brain are connected, much more than was once thought.
Sources:- UC San Francisco – official release on the study published on March 25, 2026, with a description of the mechanism by which tuft cells, enterochromaffin cells, and the vagus nerve participate in loss of appetite during parasitic infection (link)
- World Health Organization – overview of the spread and public health burden of soil-transmitted helminth infections, including data on global prevalence and consequences such as malnutrition and loss of appetite (link)
- Nature Reviews Immunology – review article on the role of acetylcholine secreted by intestinal tuft cells in defense against helminths, as the broader scientific context for the new research (link)
- Nature Reviews Microbiology – review of current knowledge on the gut-brain axis and the ways in which intestinal signals, including epithelial and neural pathways, influence brain function and behavior (link)
- Nobel Prize – official confirmation that David Julius is the winner of the 2021 Nobel Prize in Physiology or Medicine, which is relevant in the article as context about one of the leading authors of the research (link)
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