Anyone who’s had a shady oyster or a mushroom soup that didn’t sit well remembers the ominous queasiness heralding impending bad times. Bacteria release toxins that start the body’s process of speedily evacuating the contents of the stomach. It’s a protective mechanism of sorts — getting rid of the invaders en masse is probably helpful in the long term, even if it’s unpleasant in the short. But it has remained something of a mystery how the brain gets the alarm signal, then sends another one to tell the stomach to initiate a technicolor yawn.
Your next bout of food poisoning isn’t the only reason to understand this particular neural pathway. Figuring out how to counter it could be helpful for people who develop nausea caused by chemotherapy medication and other drugs. As if fighting cancer isn’t painful and scary enough, patients are often so turned off by food that keeping their weight up becomes a major struggle.
In a new study, researchers report that both bacteria and chemotherapy drugs appear to trigger the same molecular pathways in the gut. The findings, which were based on experiments with mice and published Tuesday in the journal Cell, showed that a bacterial toxin and a chemo medication both set in motion a cascade of similar neural messages that cause queasiness.
Choosing mice for the study was unusual. Mice, it turns out, can’t puke — a little foible that typically makes it difficult to use them to study nausea. Researchers have used cats and dogs in the past, but the biology of mice in general is so much better understood, with much better tools available to scientists to do so.
Cao Peng, a professor at Tsinghua University in Beijing, and his colleagues wondered whether mice might still be capable of feeling ill in the way people do after ingesting a chemo drug or a bad salad — or close enough, anyway, that researchers could use the creatures to understand the origins of the sensation.
“If we want to get better medications,” Dr. Cao said, “we need to know the detailed mechanism.”
The researchers gave the mice a bacterial toxin and watched them closely with high-speed cameras, and they found that the rodents started opening their mouths oddly after the treatment. More tests showed that their abdominal muscles were moving much like the way humans’ stomachs do when they are about to be sick. In effect, the scientists believe the mice were retching, or dry heaving. A chemo drug had the mice behaving similarly, so the scientists delved deeper into which cells were reacting to these triggers and how.
They traced the effect to certain neurons in the brain that released neurotransmitters when the drug or the toxin reached the gut. Following those messages back, they discovered cells in the small intestine that reacted to the presence of these noxious substances. A central player in the pathway to nausea and retching was an immune system molecule called interleukin 33, or IL33. Keeping mice from making IL33 significantly reduced their symptoms.
It’s possible that drugs that interfere with IL33 or other players in this pathway could help to alleviate the suffering of people having chemotherapy, Dr. Cao said. This paper — identifying behavior in mice that can stand in for vomiting and laying bare the route that signals from the gut take — is a first step in potentially improving the quality of life in chemotherapy patients, if the results hold up in humans.
Still, mice given the task of mimicking food poisoning are uncomfortable for about 24 hours after receiving bacterial toxins, Dr. Cao said. After that, they’re back to their active selves. If only we could shake off a turkey sandwich that sat out too long so quickly.