Cell: Cao Peng et al. revealed the "nausea-vomiting" brain-gut transmission neural pathway

For the first time, Cao Peng, a researcher at the Beijing Institute of Life Sciences, and collaborators have mapped detailed neural pathways in mice from the gut to the brain, which could help scientists develop better anti-vomiting drugs
for cancer patients undergoing chemotherapy.
The study was published Nov.
1 in the journal
Cell.

The urge to vomit after eating contaminated food is the body's natural defense response
to remove bacterial toxins.
Many foodborne bacteria produce toxins in the host body after ingestion, and upon sensing their presence, the brain initiates a series of biological responses, including vomiting and nausea, that clear these substances and develop an aversion
to foods that taste or look the same.

"But the details of how the signal is transmitted from the gut to the brain are unclear, because scientists have not been able to study this process
in mice.
" Cao Peng, the corresponding author of the paper, said
.

Rodents can't vomit, probably because they have long esophagus and weak muscle strength
relative to their size.
As a result, scientists have been studying vomiting in other animals such as dogs and cats, but these animals have not been fully studied and thus failed to reveal the mechanisms
of nausea and vomiting.

Cao Peng and team noticed that although the mice did not vomit, they would retch, which meant that they would also have the urge to vomit, but not vomit
.

The team found that after being infected with Staphylococcus A enterotoxin (SEA), the mice exhibited unusual mouth-opening behavior
.
SEA is a common bacterial toxin produced by Staphylococcus aureus that also causes foodborne illness
in humans.
The SEA mice opened their mouths at a wider angle than the control mice, which were fed saline
.
In addition, during the attack, the diaphragm and abdominal muscles of the SEA-treated mice contracted simultaneously, which was similar
to the pattern of dogs when vomiting.
During normal breathing, the animal's diaphragm and abdominal muscles contract
alternately.

"The neural mechanism of retching is similar
to vomiting.
In this experiment, we succeeded in establishing a sample to study toxin-induced retching in mice, through which we could observe the brain's defense response
to toxins at the molecular and cellular levels.
Cao Peng said
.

In mice treated with SEA, the team found that toxins in the gut activated enteric chromaffin cells lining the lining of the intestinal lumen to release serotonin
, a neurotransmitter.
The released serotonin binds to receptors on vagus sensory neurons located in the gut to transmit signals along the vagus nerve from the gut to a specific type of neuron, Tac1+DVC neurons, in the dorsal complex of the vagus nerve in the brainstem
.
When Cao Peng and team inactivated Tac1+ DVC neurons, SEA-treated mice retched less
than mice with normal Tac1+ DVC neuronal activity.

In addition, the team analyzed whether the chemotherapy drugs activated the same neural pathways
.
Chemotherapy drugs can also cause the recipient's defensive responses, such as nausea and vomiting
.
They injected mice with doxorubicin, a common chemotherapy drug
.
The drug made mice gag, but when the team inactivated their Tac1+ DVC neurons or serotonin complexes of their enteric chromaffin cells, the animals' retching behavior was significantly reduced
.

Cao Peng said that some current anti-vomiting drugs used in chemotherapy recipients, such as granisetron, work by blocking serotonin receptors
.
This study helps explain why the drug works
.

"With this research, we can now better understand the molecular and cellular mechanisms of nausea and vomiting, which will help us develop better drugs
.
" He said
.

Next, Cao Peng and his colleagues wanted to explore how toxins act on enteric chromaffin cells
.
Preliminary studies have shown that enteric chromaffin cells do not directly sense the presence of
toxins.
This process may involve a complex immune response
by damaged cells in the intestine.

"In addition to foodborne bacteria, humans encounter many pathogens, and our bodies have similar mechanisms to expel these toxic substances
.
For example, a cough is our body trying to clear the coronavirus
.
This is a new and exciting area of research about how the brain senses the presence of pathogens and initiates a response to clear them
.
Future research may reveal new and better drug targets, including anti-vomiting drugs
, Cao said.

Related paper information:

https://doi.
org/10.
1016/j.
cell.
2022.
10.
001