If you’re throwing up, it usually means your body is trying to get rid of a toxin. Often, it is a sign of a stomach infection.
The urge to vomit after eating contaminated food is the body’s natural defensive response to get rid of bacterial toxins. However, how our brain initiates this biological reaction upon detecting germs remains elusive.
The precise neurological pathway of the protective responses in mice from the gut to the brain has now been traced by scientists for the first time. After being consumed, many foodborne bacteria create toxins in the host. After detecting their presence, the brain will set off a cascade of biological reactions, including nausea and vomiting, to get rid of the toxins and create an aversion to similar-looking or tasting meals.
Peng Cao, the paper’s corresponding author at the National Institute of Biological Sciences in Beijing, said, “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. Rodents cannot vomit, likely because of their long esophagus and weaker muscle strength compared to their body size. As a result, scientists have been studying vomit in other animals, like dogs and cats. Still, these animals are not comprehensively studied and thus failed to reveal the mechanism of nausea and vomiting.”
Scientists discovered that although mice don’t vomit, they do retch, meaning they also get the urge to vomit but don’t do it. The scientists found that mice experienced bouts of atypical jaw opening after being exposed to Staphylococcal enterotoxin A (SEA), a common bacterial toxin produced by Staphylococcus aureus that also causes foodborne diseases in people.
Mice that received SEA opened their mouths at angles wider than those observed in the control group, where mice received saline water. Moreover, during these episodes, the diaphragm and abdominal muscles of the SEA-treated mice contract simultaneously, a pattern seen in dogs when they are vomiting. During normal breathing, animals’ diaphragm and abdominal muscles contract alternatively.
Cao said, “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. We can look into the defensive responses from the brain to toxins at the molecular and cellular levels.”
When scientists treated the mice with SEA, they found that the toxin in the intestine activates the release of serotonin, a type of neurotransmitter, by the enterochromaffin cells on the lining of the intestinal lumen.
When serotonin is released, it binds to receptors on vagal sensory neurons in the intestine, which sends messages via the vagus nerves from the gut to a particular class of Tac1+DVC neurons in the dorsal vagal complex in the brainstem. When scientists inactivated the Tac1+DVC neurons, SEA-treated mice retched less than mice with normal Tac1+DVC neuron activities.
Scientists also investigated whether chemotherapy drugs, which induce defensive responses like nausea and vomiting in recipients, activate the same neural pathway. They injected mice with doxorubicin, a common chemotherapy drug. The drug made mice retch, but when the team inactivated their Tac1+ DVC neurons or serotonin synthesis of their enterochromaffin cells, the animals’ retching behaviors were significantly reduced.
Cao said, “Some of the current anti-nausea medications for chemotherapy recipients, such as Granisetron, work by blocking the serotonin receptors. The study helps explain why the drug works.”
“With this study, we can better understand the molecular and cellular mechanisms of nausea and vomiting, which will help us develop better medications.”
- Zhiyong Xie, Xianying Zhang, Miao Zhao, Lifang Huo, Meizhu Huang, Dapeng Li, Shuangfeng Zhang, Xinyu Cheng, Huating Gu, Chen Zhang, Cheng Zhan, Fengchao Wang, Congping Shang, Peng Cao. The gut-to-brain axis for toxin-induced defensive responses. Cell, 2022; DOI: 10.1016/j.cell.2022.10.001