Cell: Chinese scientists reveal the neural pathway for vomiting after eating infected food

The urge to vomit after eating contaminated food is the body's natural defense response
to get rid of bacterial toxins.
However, the process by which our brains initiate this biological response after detecting germs remains elusive
.
In a new study, researchers from China's Beijing Institute of Life Sciences, Tsinghua University, Guangzhou Medical University, University of Science and Technology of China, Capital Medical University, and Fudan University have mapped for the first time detailed neural pathways
in mouse defense responses from the gut to the brain.
The discovery could help scientists develop better anti-nausea drugs
for cancer patients undergoing chemotherapy.
The findings were published in the November 10, 2022 issue of the journal Cell under the title "The gut-to-brain axis for toxin-induced defensive responses.
"

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

Dr.
Peng Cao, co-corresponding author of the paper and from the Beijing Institute of Life Sciences, said, "But the details of how this signal is transmitted from the gut to the brain are not clear, because scientists cannot study this process
in mice.
" "Rodents can't vomit, probably because they have long esophagus and weak muscle strength compared to their body 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 therefore failed to reveal the mechanisms
of nausea and vomiting.

Cao and his team noticed that while the mice didn't vomit, they did retch--- meaning they also had the urge to vomit, but not vomit
.
The team found that after receiving staphylococcal enterotoxin A (SEA), mice developed abnormal mouth opening, a common bacterial toxin produced by Staphylococcus aureus that also causes foodborne illness
in humans.

Mice receiving SEA opened their mouths at a wider angle than was observed in control mice, which received saline
.
In addition, during mouth opening, the diaphragm muscles and abdominal muscles of the SEA-treated mice contracted simultaneously, a pattern
observed when dogs vomited.
During normal breathing, the animal's diaphragm muscles and abdominal muscles contract
alternately.

Cao said, "The neural mechanism of retching is similar
to the neural mechanism of vomiting.
In this experiment, we successfully established a model for studying toxin-induced retching in mice, through which we could study the brain's defense response
to toxins at the molecular and cellular levels.
”

In SEA-treated mice, the authors found that SEA in the gut activated enterochromaffin cells on the lining of the intestinal lumen to release the neurotransmitter serotonin
.
The released serotonin binds to receptors on vagus sensory neurons located in the gut, which carry these signals along the vagus nerve from the gut to specific types of neurons ----Tac1+DVC neurons
in the dorsal complex of the vagus nerve of the brainstem.
When Cao and his team inactivated Tac1+DVC neurons, SEA-treated mice had less
retching than mice with normal Tac1+ DVC neuronal activity.

Image from Cell, 2022, doi:10.
1016/j.
cell.
2022.
10.
001
.

In addition, the team investigated whether chemotherapy drugs activate the same neural pathways in which these drugs also induce defensive responses
such as nausea and vomiting in patients.
They injected mice with doxorubicin, a common chemotherapy drug
.
The drug made the mice gagg, but their retching behavior was significantly reduced
when they inactivated the release of serotonin from their Tac1+ DVC neurons or their enteric chromaffin cells.

Cao said some current anti-nausea drugs for patients treated with chemotherapy, such as granisetron, work by blocking serotonin receptors
.
This new study helps explain why granisetron works
.

"With this new study, we are now able to better understand the molecular and cellular mechanisms of nausea and vomiting, which will help us develop better drugs
," Cao said.
”

As a next step, Cao and his colleagues hope to explore how the toxin acts on enteric chromaffin cells
.
Preliminary studies have shown that enteric chromaffin cells do not directly perceive the presence of
toxins.
This process may involve a complex immune response
by damaged cells in the gut.

"In addition to foodborne germs, humans encounter a lot of pathogens, and our bodies are equipped with similar mechanisms to expel these toxic substances
," Cao said.
For example, coughing is our body's attempt to
clear the coronavirus.
Targeting how the brain senses the presence of pathogens and initiates a response to get rid of them is a new and exciting area of research
.
He added that future studies may discover new and better targets for developing drugs, including anti-nausea drugs
.
(Biovalley Bioon.
com)

Resources:

Zhiyong Xie et al.
 The gut-to-brain axis for toxin-induced defensive responses, Cell, 2022, doi:10.
1016/j.
cell.
2022.
10.
001.