The desire to vomit after eating unsafe food is the body’s natural defense response to cleanse itself of bacterial toxins.
However, the mechanism by which our brain starts this biological response after identifying the germs is still a mystery.
For the first time, scientists drew a detailed map of how the nerves in mice send defensive signals from the gut to the brain.
The findings, published in the journal Cell today, may help in the improvement of chemotherapy-related nausea treatments for cancer patients.
Toxins are produced by the host after eating of many food-borne bacteria. After detecting their presence, the brain will trigger a series of biological responses, such as vomiting and feeling sick, to get rid of the substances and make the body dislike foods that taste or look the same.
The National Institute of Biological Sciences in Beijing’s Peng Cao, the paper’s corresponding author, notes that because scientists were unable to research the procedure on mice, the specifics of how the signals are carried from the gut to the brain were unclear.
Because of their long esophagus and lesser muscle strength in relation to their body size, rodents are unable to vomit. As a result, scientists have been examining the vomit of other species, such as dogs and cats, but because these creatures are not thoroughly examined, they have not been able to identify the process underlying nausea and vomiting.
Cao and his team discovered that while mice do not vomit, they do retch, which indicates that they also have the impulse to vomit but do not really do so.
Mice had bouts of atypical mouth opening after receiving Staphylococcal enterotoxin A (SEA), a common bacterial toxin generated by Staphylococcus aureus that also causes foodborne diseases in people.
When mice were given SEA, their mouths opened wider than when they were given salt water, which was used as a control.
In addition, during these episodes, the diaphragm and abdominal muscles of SEA-treated mice contract concurrently, a pattern observed in vomiting dogs.
When an animal breathes normally, their diaphragm and abdominal muscles contract in turn.
“The neural mechanism of retching,” according to Cao, “is similar to that of vomiting. In this experiment, we successfully build a paradigm for studying toxin-induced retching in mice, with which we can look into the defensive responses from the brain to toxins at the molecular and cellular levels.”
The team found that when SEA was given to mice, the toxin in the intestine caused the enterochromaffin cells that line the inside of the intestine to release serotonin, which is a type of neurotransmitter.
The released serotonin binds to receptors on vagal sensory neurons in the intestine, which conveys signals along the vagus nerves from the gut to Tac1+DVC neurons in the dorsal vagal complex of the brainstem.
When Cao and his team turned off the Tac1+DVC neurons, mice that had been given SEA retched less than mice whose Tac1+DVC neurons were working normally.
The team also looked into whether chemotherapy drugs, which can cause recipients to experience defensive reactions like nausea and vomiting, trigger the same brain system.
They gave mice an injection of the chemotherapy drug doxorubicin. The medication caused the mice to vomit, but the team found that the behavior was greatly diminished when the Tac1+ DVC neurons or serotonin synthesis of the enterochromaffin cells were deactivated.
Cao says that some anti-nausea drugs for people who are getting chemotherapy, like Granisetron, work by blocking the serotonin receptors. The study helps explain how 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 medications,” Cao adds.
Next, Cao and his colleagues want to find out how toxins affect enterochromaffin cells. Early research shows that enterochromaffin cells don’t directly pick up on the presence of toxins.
The procedure most likely involves intricate immune reactions to harmed intestinal cells.
Humans come into contact with a variety of pathogens in addition to foodborne germs, and our bodies are designed with similar processes to eliminate these hazardous agents. For instance, our body uses coughing to try and get rid of the coronavirus.
The study of how the brain detects the presence of pathogens and launches defense mechanisms against them is a recent and fascinating area of study.
According to Cao, future study might identify new, more effective pharmacological targets, such as those for anti-nausea medications.
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