Summary: After ingestion of contaminated food, toxins activate the secretion of serotonin by entero-enteric cells on the lining of the intestinal lumen. Serotonin binds to receptors on vagus sensory neurons in the gut, and transmits signals along the vagus nerve to neurons in the dorsal vagus complex, resulting in retching behaviors.

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The urge to vomit after eating contaminated food is the body’s natural defense response to getting rid of bacterial toxins. However, the process of how our brain initiates this biological reaction when germs are detected remains elusive.

For the first time, researchers have mapped the detailed neural pathway of defensive responses from the gut to the brain in mice.

The study was presented November 1 in the journal cellIt could help scientists develop better anti-nausea drugs for cancer patients undergoing chemotherapy.

Many foodborne bacteria produce toxins in the host after they have been ingested. The brain, after sensing their presence, will initiate a series of biological responses, including vomiting and nausea, to get rid of substances and develop an aversion to foods that taste or look the same.

“But the details about how the signals are transmitted from the gut to the brain were not clear, because scientists were unable to study the process in mice,” says Bing Kao, corresponding author of the research paper at the National Institute of Biological Sciences in Beijing. Rodents cannot vomit, likely due to the length of the esophagus and poor muscle tone compared to body size.

As a result, scientists have been studying vomiting in other animals such as dogs and cats, but these animals have not been comprehensively studied and thus failed to reveal the mechanism of nausea and vomiting.

Kao and his team note that while the mice do not vomit, they vomit—which means they also feel the need to vomit without vomiting.

The team found that after receiving Staphylococcus enterotoxin A (SEA), a common bacterial toxin produced by Staphylococcus aureus that also leads to foodborne illnesses in humans, the mice had episodes of unusually open mouth.

Mice that received SEA opened their mouths at wider angles than those observed in the control group, where rats received saline. Moreover, during these episodes, the diaphragm and abdominal muscles of SEA-treated mice contract simultaneously, a pattern seen in dogs when vomiting. During normal breathing, an animal’s diaphragm and abdominal muscles alternately contract.

“The neural mechanism of retching is similar to that of vomiting. In this experiment, we succeeded in building a model to study toxin-induced retaliation in mice, with which we can look at defensive responses from the brain to toxins at both the molecular and cellular levels.”

In mice treated with SEA, the team found that the toxin in the intestine activated the release of serotonin, a type of neurotransmitter, by enterochromaffin cells on the lining of the intestinal lumen.

Released serotonin binds to receptors on vagus sensory neurons in the gut, which transmit signals along vagus nerves from the gut to a specific type of neuron in the dorsal vagus complex — Tac1+DVC neurons — in the brainstem.

When Kao and his team disrupted Tac1+DVC neurons, SEA-treated mice shrank less compared to mice with normal Tac1+DVC neuronal activities.

In addition, the team investigated whether chemotherapy drugs, which also induce defensive reactions such as nausea and vomiting in recipients, activate the same neural pathway.

This is a cartoon of a man holding his stomach
Many foodborne bacteria produce toxins in the host after they have been ingested. The image is in the public domain

They injected mice with doxorubicin, a common chemotherapy drug. The drug made the mice squirm, but when the team disrupted Tac1+ DVC neurons or serotonin synthesis for their intestinal cells, the animals’ retching behaviors dramatically decreased.

Cao says that some of the current anti-nausea medications for chemotherapy recipients, such as Granisetron, work by blocking serotonin receptors. The study helps explain why the drug works.

“With this study, we can now better understand the molecular and cellular mechanisms of nausea and vomiting, which will help us develop better drugs,” Kao says.

Next, Kao and his colleagues want to explore how toxins affect intestinal cells. Preliminary research shows that enterochromaffin cells do not sense the presence of toxins directly. The process likely involves complex immune responses to damaged cells in the intestine.

“In addition to foodborne germs, humans encounter many pathogens, and our body is equipped with similar mechanisms to expel these toxic substances.

“For example, coughing is our bodies’ attempt to clear the coronavirus. It is an exciting new area of ​​research on how the brain senses the presence of pathogens and initiates responses to get rid of them,” Kao says, adding that future research may reveal new and better targets for drugs, including anti-nausea drugs. .

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About this Neuroscience Research News

author: press office
source: Click on the cell
Contact: Press Office – Cell Press
picture: The image is in the public domain

original search: open access.
“The gut-to-brain hub of toxin-induced defensive responses” by Peng Cao et al. cell


The gut-brain hub for toxin-induced defensive responses


  • Mice show nausea and retching due to bacterial toxins and chemotherapy drugs
  • Identification of the gut-brain circuit molecularly specific for nausea and retching
  • Distinctive brainstem circuits cause nausea and retching
  • Toxin-induced signaling can be mediated via an immunoendocrine axon in the gut


After eating food contaminated with toxins, the brain initiates a series of defensive responses (such as nausea, retching, and vomiting). The way in which the brain detects ingested toxins and coordinates diverse defensive responses is still poorly understood.

Here, we developed a mouse-based model to study defense responses induced by bacterial toxins. Using this model, we have identified a set of molecularly defined gut and brain circuits that jointly mediate toxin-induced defensive responses.

The alimentary canal circuit consists of a subset of Htr3a+ vagus sensory neurons that transmit toxin-related signals from the gastro-intestinal cells to tak 1+ Neurons in the dorsal vagus complex (DVC).

tak 1+ DVC neurons drive tremor-like behavior and conditioned flavor avoidance through divergent projections of the rostral ventral respiratory group and the lateral lateral nucleus, respectively. Manipulation of these circuits also interferes with the defensive responses induced by the chemotherapy drug doxorubicin.

These results indicate that food poisoning and chemotherapy recruit similar circuit units to initiate defensive responses.

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