Washington: The body's natural defensive mechanism to get rid of bacterial toxins is the urge to vomit after eating tainted food. But the mechanism by which our brain starts this biological response after sensing the germs is still a mystery. Researchers have created a detailed neural map of the defensive responses in mice from the gut to the brain for the first time.
The study, published in the journal Cell, may aid in the improvement of chemotherapy-related nausea treatments for cancer patients. After being consumed, many foodborne bacteria produce toxins in the host. When the brain detects them, it will set off a chain of biological reactions, including nausea and vomiting, to get rid of the substances and create an aversion to similar-tasting or-looking foods.
"But details on how the signals are transmitted from the gut to the brain were unclear, because scientists couldn't study the process on mice," says Peng Cao, the paper's corresponding author at the National Institute of Biological Sciences in Beijing.
Rodents cannot vomit, likely because of their long oesophagus and weaker muscle strength compared to their body size. As a result, scientists have been studying vomit in other animals like dogs and cats, but these animals are not comprehensively studied and thus failed to reveal the mechanism of nausea and vomiting.
Cao and his team discovered that while mice do not vomit, they do retch, which indicates that they also have the urge to vomit but do not actually do so. The researchers discovered that mice experienced episodes of unusual mouth opening after being exposed to Staphylococcal enterotoxin A (SEA), a common bacterial toxin produced by Staphylococcus aureus that also causes foodborne illnesses in humans.
The mouths of the mice who received SEA opened at wider angles than the mouths of the mice in the control group, which received saline water. Additionally, the SEA-treated mice experience these episodes with simultaneous contractions of their diaphragm and abdominal muscles, a pattern similar to that of vomiting dogs. Animals' diaphragm and abdominal muscles alternately contract during normal breathing.
"The neural mechanism of retching 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," Cao says.
Researchers discovered that serotonin, a type of neurotransmitter, is released by enterochromaffin cells on the lining of the intestinal lumen when SEA is administered to mice. The signal is sent from the gut along the vagus nerves to a particular class of neurons in the dorsal vagal complex--Tac1+DVC neurons--in the brainstem by binding to receptors on the vagal sensory neurons in the intestine. SEA-treated mice retched less than mice with normal Tac1+DVC neuron activities did when Cao and his team inactivated the Tac1+DVC neurons.
The team also looked into whether chemotherapy drugs, which also cause recipients to experience defensive reactions like nausea and vomiting, activate the same neural pathway. A typical chemotherapy drug called doxorubicin was injected into mice. The medication caused the mice to vomit, but the team found that the behaviour was significantly diminished when the Tac1+ DVC neurons or serotonin synthesis of the enterochromaffin cells were deactivated.
Some of the current anti-nausea drugs for chemotherapy patients, like Granisetron, according to Cao, function by blocking the serotonin receptors. The study explains how the medication functions. "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 says.
Next, Cao and his colleagues want to explore how toxins act on enterochromaffin cells. Preliminary research shows that enterochromaffin cells don't sense the presence of toxins directly. The process likely involves complex immune responses of damaged cells in the intestine.
"In addition to foodborne germs, humans encounter a lot of pathogens, and our body is equipped with similar mechanisms to expel these toxic substances. For example, coughing is our body's attempt to remove the coronavirus. It's a new and exciting field of research about how the brain senses the existence of pathogens and initiates responses to get rid of them." Cao says, adding that future research may reveal new and better targets for drugs, including anti-nausea medicines. (ANI)
