2026-03-31
When immunity suppresses appetite: decoding a gut–brain dialogue
Gastroenterology and Hepatology
By Elodie Vaz | Published on March 31, 2026 | 4 min read
Loss of appetite is a common symptom during intestinal infections, whether acute—such as gastroenteritis—or chronic, particularly in parasitic infections. Although well documented, the precise biological mechanisms behind this phenomenon have remained poorly understood. How does the immune system, in response to infection, alter such a fundamental behavior as eating?
A study conducted by researchers at UC San Francisco, published on March 25 in Nature, provides new insight into this question. The objective was to identify the molecular mechanisms linking the intestinal immune response to the brain, in order to explain how infection can induce appetite loss.
As Professor and study author David Julius explained in a press release: “The question we wanted to answer was not only how the immune system fights parasites, but also how it engages the nervous system to change behavior.” He added: “It turns out there is a very elegant molecular logic behind this.”
The researchers focused on two rare intestinal cell populations: tuft cells, involved in detecting parasites and initiating immune responses, and enterochromaffin (EC) cells, known for releasing neuroactive signals.
Until now, the functional link between these two cell types had not been clearly established. “My lab has long been interested in how tuft cells, after their initial response to parasitic infection, release signals to other cell types,” noted Professor and co-author Richard Locksley.
Using experimental approaches combining genetically modified cells and tissue cultures, the researchers identified a precise signaling pathway. When tuft cells detect parasitic metabolites such as succinate, they release acetylcholine.
This neurotransmitter then acts on EC cells, triggering the release of serotonin. Serotonin activates vagal nerve fibers, which transmit the signal to the brain, ultimately leading to changes in feeding behavior.
“We found that tuft cells perform a function similar to neurons, but through a completely different mechanism,” explained Dr. Koki Tohara. “They use acetylcholine to communicate, but without any of the typical cellular machinery neurons require to release it.”
The study also highlights a key temporal aspect. Tuft cells release acetylcholine in two phases: an initial brief release, followed by a prolonged phase once the immune response is fully activated and these cells proliferate.
This mechanism explains why appetite loss does not occur immediately. “It explains why you feel fine at first, and then begin to feel unwell as the infection progresses,” said David Julius. “The gut essentially waits to confirm that the threat is real and persistent before signaling the brain to change behavior.”
In vivo validation of the mechanism
To confirm these findings, researchers studied mice infected with parasitic worms. Animals with functional tuft cells showed a progressive decrease in food intake. In contrast, mice unable to produce acetylcholine via these cells maintained normal feeding behavior, confirming the central role of this signaling pathway.
These results open new therapeutic perspectives. “Controlling tuft cell activity could be a way to regulate some of the physiological responses associated with these infections,” noted Richard Locksley.
More broadly, this communication pathway may be involved in other conditions. Since tuft cells are present in multiple organs, dysfunction of this circuit could contribute to disorders such as irritable bowel syndrome, food intolerances, or certain chronic visceral pain conditions.
This study reveals a direct and structured dialogue between the immune and nervous systems, reshaping our understanding of the gut–brain axis. It suggests that behaviors such as appetite loss are not merely side effects of illness, but finely regulated adaptive responses.
In the long term, targeting this pathway could help modulate debilitating symptoms associated with many diseases—highlighting once again how increasingly interconnected the fields of immunology, neuroscience, and physiology have become.
About the Author – Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on human life. A registered nurse since 2010, she spent twelve years at patients’ bedsides before exchanging her stethoscope for a notebook. She now investigates the links between environment and health, convinced that the vitality of life cannot be reduced to that of humans alone.
Loss of appetite is a common symptom during intestinal infections, whether acute—such as gastroenteritis—or chronic, particularly in parasitic infections. Although well documented, the precise biological mechanisms behind this phenomenon have remained poorly understood. How does the immune system, in response to infection, alter such a fundamental behavior as eating?
A study conducted by researchers at UC San Francisco, published on March 25 in Nature, provides new insight into this question. The objective was to identify the molecular mechanisms linking the intestinal immune response to the brain, in order to explain how infection can induce appetite loss.
As Professor and study author David Julius explained in a press release: “The question we wanted to answer was not only how the immune system fights parasites, but also how it engages the nervous system to change behavior.” He added: “It turns out there is a very elegant molecular logic behind this.”
Two cell types at the heart of the dialogue
The researchers focused on two rare intestinal cell populations: tuft cells, involved in detecting parasites and initiating immune responses, and enterochromaffin (EC) cells, known for releasing neuroactive signals.
Until now, the functional link between these two cell types had not been clearly established. “My lab has long been interested in how tuft cells, after their initial response to parasitic infection, release signals to other cell types,” noted Professor and co-author Richard Locksley.
A newly identified molecular cascade
Using experimental approaches combining genetically modified cells and tissue cultures, the researchers identified a precise signaling pathway. When tuft cells detect parasitic metabolites such as succinate, they release acetylcholine.
This neurotransmitter then acts on EC cells, triggering the release of serotonin. Serotonin activates vagal nerve fibers, which transmit the signal to the brain, ultimately leading to changes in feeding behavior.
“We found that tuft cells perform a function similar to neurons, but through a completely different mechanism,” explained Dr. Koki Tohara. “They use acetylcholine to communicate, but without any of the typical cellular machinery neurons require to release it.”
Explaining the delayed response
The study also highlights a key temporal aspect. Tuft cells release acetylcholine in two phases: an initial brief release, followed by a prolonged phase once the immune response is fully activated and these cells proliferate.
This mechanism explains why appetite loss does not occur immediately. “It explains why you feel fine at first, and then begin to feel unwell as the infection progresses,” said David Julius. “The gut essentially waits to confirm that the threat is real and persistent before signaling the brain to change behavior.”
In vivo validation of the mechanism
To confirm these findings, researchers studied mice infected with parasitic worms. Animals with functional tuft cells showed a progressive decrease in food intake. In contrast, mice unable to produce acetylcholine via these cells maintained normal feeding behavior, confirming the central role of this signaling pathway.
Beyond parasitic infections
These results open new therapeutic perspectives. “Controlling tuft cell activity could be a way to regulate some of the physiological responses associated with these infections,” noted Richard Locksley.
More broadly, this communication pathway may be involved in other conditions. Since tuft cells are present in multiple organs, dysfunction of this circuit could contribute to disorders such as irritable bowel syndrome, food intolerances, or certain chronic visceral pain conditions.
Toward a new understanding of the gut–brain axis
This study reveals a direct and structured dialogue between the immune and nervous systems, reshaping our understanding of the gut–brain axis. It suggests that behaviors such as appetite loss are not merely side effects of illness, but finely regulated adaptive responses.
In the long term, targeting this pathway could help modulate debilitating symptoms associated with many diseases—highlighting once again how increasingly interconnected the fields of immunology, neuroscience, and physiology have become.
Read next: When the hippocampus drives our cravings
About the Author – Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on human life. A registered nurse since 2010, she spent twelve years at patients’ bedsides before exchanging her stethoscope for a notebook. She now investigates the links between environment and health, convinced that the vitality of life cannot be reduced to that of humans alone.
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