The urge to vomit after eating contaminated food is the body’s natural defensive response to get rid of bacterial toxins


Nausea and vomiting are common gastrointestinal complaints that can be triggered by diverse emetic stimuli through central and/or peripheral nervous systems.

Both nausea and vomiting are considered as defense mechanisms when threatening toxins/drugs/bacteria/viruses/fungi enter the body either via the enteral (e.g., the gastrointestinal tract) or parenteral routes, including the blood, skin, and respiratory systems. 

The urge to vomit after eating contaminated food is the body’s natural defensive response to get rid of bacterial toxins. However, the process of how our brain initiates this biological reaction upon detecting the germs remains elusive.

For the first time, researchers mapped out the detailed neural pathway of the defensive responses from the gut to the brain in mice.

The study, presented November 1 in the journal Cell, could help scientists develop better anti-nausea medications for cancer patients who undergo chemotherapy.

Many foodborne bacteria produce toxins in the host after being ingested. The brain, after sensing their presence, will initiate a series of biological responses, including vomit and nausea, to get rid of the substances and develop an aversion toward foods that taste or look the same.

“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 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, but these animals are not comprehensively studied and thus failed to reveal the mechanism of nausea and vomiting.

Cao and his team noticed that while mice don’t vomit, they retch – meaning they also experience the urge to vomit without throwing up.

The team found that after receiving Staphylococcal enterotoxin A (SEA), which is a common bacterial toxin produced by Staphylococcus aureus that also leads to foodborne illnesses in humans, mice developed episodes of unusual mouth opening.

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.

“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.

In mice treated with SEA, the team found 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.

The released serotonin binds to the receptors on the vagal sensory neurons located in the intestine, which transmits the signals along the vagus nerves from the gut to a specific type of neurons in the dorsal vagal complex—Tac1+DVC neurons—in the brainstem.

When Cao and his team inactivated the Tac1+DVC neurons, SEA-treated mice retched less compared with mice with normal Tac1+DVC neuron activities.

In addition, the team investigated whether chemotherapy drugs, which also 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 says 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 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.

Nausea and vomiting are essential protective defense processes by which humans as well as vomit-competent animals tend to avoid ingestion and/or digestion of potentially toxic substances. Nausea is the unpleasant sensation of having the urge to vomit, whereas vomiting (emesis) is a physical event and is the forceful expulsion of intestinal and gastric contents through the mouth [1].

Vomiting is often preceded by retching, where the content of gastrointestinal tract is forced into the esophagus, without expulsion of the vomitus [1]. Oftentimes, nausea and vomiting occur on a temporal continuum, but this is not always the case. Sometimes, severe nausea can be present without emesis, and, less frequently, vomiting may be present without nausea. Thus, nausea is no longer considered only a penultimate step of vomiting [2].

Nausea and vomiting can be triggered by several mechanisms, as depicted in Figure 1, including:

(i) toxins/drugs/bacteria/viruses/fungi that enter the lumen of the gastrointestinal and, subsequently, indirectly stimulate the brainstem emetic nuclei located in the dorsal vagal complex via release of local emetic neurotransmitters in the upper gastrointestinal tract and subsequent activation of corresponding receptors present on vagus nerves and/or splanchnic nerves;

(ii) toxic agents/drugs or infectious organisms that enter the body systemically and that may act directly on the dorsal vagal complex emetic nuclei in the brainstem;

(iii) pathologies in the gastrointestinal tract, which stimulate vagal afferents or other visceral organs (e.g., cardiac), which stimulate visceral afferents;

(iv) emotional and cognitive stimuli within the central nervous system (CNS), including cerebral cortex and the limbic system; and

(v) disturbances of the vestibular nuclei and cerebellum in motion sickness [3,4,5,6,7,8]. The processes of nausea and vomiting result from continuous interactions between the gastrointestinal tract, including its enteric nervous system, the CNS, and the autonomic nervous system [9,10].

Figure 1
Central and peripheral anatomical sites involved in nausea and vomiting induced by various stimuli. Nausea and vomiting can be generated by diverse stimuli and are mediated by the bidirectional interaction between brain and gut. In brief: (1) The brainstem area postrema in the floor of the fourth ventricle lacks blood brain barrier and thus serves as direct central receptor sites for circulating and systemic emetic stimuli in the cerebrospinal fluid and the blood [11]. (2) Systemically administered drugs can activate corresponding receptors present on vagal afferents, which project sensory signals to the nucleus of the solitary tract [11,12]. (3) Peripheral stimuli such as toxic drugs and microbials (e.g., bacteria, viruses, fungi) that enter the lumen of the gastrointestinal tract (GIT) and pathologies in the GIT cause release of local emetic neurotransmitters/modulators, which subsequently act on the corresponding receptors present on vagal afferents and/or stimulate the brainstem area postrema via circulating blood [9,10]. Besides the area postrema and the sensory vagal afferents, the nucleus of the solitary tract is also the recipient of: (i) direct neural inputs from the splanchnic nerves carrying sensation caused by diseases of visceral organs (e.g., cardiac, kidney); (ii) brainstem vestibular nuclei collecting signals from vestibular apparatus in inner ear and/or cerebellum, caused by stimuli related to motion sickness and opioid analgesics [13,14]; and (iii) the cerebral cortex and limbic system, which accept and process emotional and cognitive stimuli [3,4,5,6,7,8]. The nucleus of the solitary tract has output pathways to the dorsal motor nucleus of the vagus, which further project to the upper gastrointestinal tract to produce the vomiting reflex [11]. In addition, the nucleus of the solitary tract has projections to the mid- and forebrain for the perception of nausea [15].

reference link :

Original Research: Open access.
The gut-to-brain axis for toxin-induced defensive responses” by Peng Cao et al. Cell


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