Tag Archives: Toxin

Microbiology

Identifying what makes some gut bacteria strains life-threatening in pre-term babies

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Reviewed by Megan Craig, M.Sc.May 25 2023

Researchers from the Quadram Institute and University of East Anglia have identified what makes some strains of gut bacteria life-threatening in pre-term babies.

The findings will help identify and track dangerous strains and protect vulnerable neonatal babies.

A major threat to neonatal babies with extremely low birth weight is necrotizing enterocolitis (NEC).

Rare in full-term babies, this microbial infection exploits vulnerabilities destroying gut tissue leading to severe complications. Two out of five cases are fatal.

One bacterial species that causes especially sudden and severe disease is Clostridium perfringens. These are common in the environment and non-disease-causing strains live in healthy human guts.

So what makes certain strains so dangerous in preterm babies?

Prof Lindsay Hall and Dr Raymond Kiu from the Quadram Institute and UEA led the first major study on C. perfringens genomes from preterm babies, including some babies with necrotizing enterocolitis.

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The research team analyzed C. perfringens genomes from the faecal samples of 70 babies admitted to five UK Neonatal Intensive Care Units (NICUs).

Based on genomic similarities, they found one set had a lower capacity to cause disease. This allowed a comparison with the more virulent strains.

The less virulent group lacked genes responsible for production of a toxin called PFO and other factors needed for colonization and survival.

This study has begun to construct genomic signatures for C. perfringens associated with healthy preterm babies and those with necrotizing enterocolitis.

Exploring genomic signatures from hundreds of Clostridium perfringens genomes has allowed us potentially to discriminate between ‘good’ bacterial strains that live harmlessly in the preterm gut, and ‘bad’ ones associated with the devastating and deadly disease necrotizing enterocolitis.

We hope the findings will help with ‘tracking’ deadly C. perfringens strains in a very vulnerable group of patients – preterm babies.”

Prof Lindsay Hall, UEA’s Norwich Medical School and the Quadram Institute

Larger studies, across more sites and with more samples may be needed but this research could help identify better ways to control necrotizing enterocolitis.

The team previously worked alongside Prof Paul Clarke and clinical colleagues at the Norfolk and Norwich University Hospital NICU. And they demonstrated the benefits of providing neonatal babies with probiotic supplements.

The enterocolitis gut microbiome of neonatal infants is significantly disrupted, making it susceptible to C. perfringens overgrowth.

Prof Hall said: “Our genomic study gives us more data that we can use in the fight against bacteria that cause disease in babies – where we are harnessing the benefits of another microbial resident, Bifidobacterium, to provide at-risk babies with the best possible start in life.”

Dr Raymond Kiu, from the Quadram Institute, said: “Importantly, this study highlights Whole Genome Sequencing as a powerful tool for identifying new bacterial lineages and determining bacterial virulence factors at strain level which enables us to better understand disease.”

This research was supported by the Biotechnology and Biological Sciences Research Council, part of UKRI, and the Wellcome Trust.

The study was led by researchers at Quadram Institute and the University of East Anglia, in collaboration with colleagues at Imperial College, London, the University of Glasgow, the University of Cambridge, Newcastle University and Northumbria University.

‘Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains’ is published in Nature Microbiology.

Source:

University of East Anglia

Journal reference:

Kiu, R., et al. (2023). Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains. Nature Microbiology. doi.org/10.1038/s41564-023-01385-z.

Microbiology

Some bacteria cells get hangry too, study finds

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Reviewed by Emily Henderson, B.Sc.Apr 3 2023

Have you ever been so hungry that you become angry, otherwise known as “hangry?” New research by Adam Rosenthal, PhD, assistant professor in the Department of Microbiology and Immunology, has found that some bacteria cells get hangry too, releasing harmful toxins into our bodies and making us sick.

Rosenthal and his colleagues from Harvard, Princeton and Danisco Animal Nutrition discovered, using a recently developed technology, that genetically identical cells within a bacterial community have different functions, with some members behaving more docile and others producing the very toxins that make us feel ill.

Bacteria behave much more different than we traditionally thought. Even when we study a community of bacteria that are all genetically identical, they don’t all act the same way. We wanted to find out why.”

Adam Rosenthal, PhD, Assistant Professor, Department of Microbiology and Immunology

The findings, published in Nature Microbiology, are particularly important in understanding how and why bacterial communities defer duties to certain cells – and could lead to new ways to tackle antibiotic tolerance further down the line.

Rosenthal decided to take a closer look into why some cells act as “well-behaved citizens” and others as “bad actors” that are tasked with releasing toxins into the environment. He selected Clostridium perfringens – a rod-shaped bacterium that can be found in the intestinal tract of humans and other vertebrates, insects, and soil – as his microbe of study.

With the help of a device called a microfluidic droplet generator, they were able to separate, or partition, single bacterial cells into droplets to decode every single cell.

They found that the C. perfringens cells that were not producing toxins were well-fed with nutrients. On the other hand, toxin-producing C. perfringens cells appear to be lacking those crucial nutrients.

“If we give more of these nutrients,” postulated Rosenthal, “maybe we can get the toxin-producing cells to behave a little bit better.”

Researchers then exposed the bad actor cells to a substance called acetate. Their hypothesis rang true. Not only did toxin levels drop across the community, but the number of bad actors reduced as well. But in the aftermath of such astounding results, even more questions are popping up.

Now that they know that nutrients play a significant role in toxicity, Rosenthal wonders if there are particular factors found in the environment that may be ‘turning on’ toxin production in other types of infections, or if this new finding is only true for C. perfringens.

Perhaps most importantly, Rosenthal theorizes that introducing nutrients to bacteria could provide a new alternative treatment for animals and humans, alike.

For example, the model organism Clostridium perfringens is a powerful foe in the hen house. As the food industry is shifting away from the use of antibiotics, poultry are left defenseless from the rapidly spreading, fatal disease. The recent findings from Rosenthal et al. may give farmers a new tool to reduce pathogenic bacteria without the use of antibiotics.

As for us humans, there is more work to be done. Rosenthal is in the process of partnering with colleagues across UNC to apply his recent findings to tackle antibiotic tolerance. Antibiotic tolerance occurs when some bacteria are able to dodge the drug target even when the community has not evolved mutations to make all cells resistant to an antibiotic. Such tolerance can result in a less-effective treatment, but the mechanisms controlling tolerance are not well understood.

In the meantime, Rosenthal will continue to research these increasingly complex bacterial communities to better understand why they do what they do.

Source:

University of North Carolina Health Care

Journal reference:

McNulty, R., Sritharan, D., Pahng, S. H., Meisch, J. P., Liu, S., Brennan, M. A., Saxer, G., Hormoz, S., & Rosenthal, A. Z. (2023). Probe-based bacterial single-cell RNA sequencing predicts toxin regulation. Nature Microbiology. doi.org/10.1038/s41564-023-01348-4.

Microbiology

Vaccinating against toxin produced by E. coli may protect against malnutrition and stunting

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Reviewed by Emily Henderson, B.Sc.Jan 9 2023

Diarrhea is no longer the killer it was in the mid-20th century, when an estimated 4.5 million children under age 5 died of it every year. While lifesaving oral rehydration therapy turned the tide, it doesn’t prevent infection. Millions of children in low- and middle-income countries still endure repeated bouts of diarrhea that weaken their bodies and leave them vulnerable to malnutrition and stunted growth, and less able to fight off a wide range of infections.

Researchers at Washington University School of Medicine in St. Louis have determined, in studies of human cells as well as mice, how some types of diarrhea-causing Escherichia coli (E. coli) bacteria damage the intestines to cause malnutrition and stunting. And they’ve shown that vaccinating against a toxin produced by E. coli protects infant mice from intestinal damage.

The findings suggest that a vaccine against this kind of E. coli could boost global efforts to ensure that all children not only make it to age 5, but thrive. The study is available online in Nature Communications.

“Ideally, we’d like to have a vaccine that prevents acute diarrhea, which still kills half a million children a year, and that also protects against long-term effects such as malnutrition, which is perhaps the bigger part of the problem now,” said senior author James M. Fleckenstein, MD, a professor of medicine and of molecular microbiology. “When kids become malnourished, their risk of dying from any cause goes up. The World Health Organization is in the process of deciding how to prioritize vaccines for kids in low- and middle-income countries, and I think these data suggest that vaccinating kids against E. coli diarrhea could be hugely beneficial in places that struggle with this.”

Fleckenstein studies a kind of E. coli known as enterotoxigenic E. coli, or ETEC -; so named for the two toxins it produces -; and its effects on children who live where the bacteria run rampant. E. coliis a common cause of diarrhea worldwide, but the strains found in the U.S. and other high-income countries typically don’t carry the same toxins as those in low- and middle-income countries. And that may make all the difference.

A 2020 study by Fleckenstein and Alaullah Sheikh, PhD -; then a postdoctoral researcher in Fleckenstein’s lab and now an instructor in medicine -; indicated that one of ETEC’s two toxins, heat-labile toxin, does more than trigger a case of the runs. The toxin also affects gene expression in the gut, ramping up genes that help the bacteria stick to the gut wall.

As part of the latest study, Fleckenstein and Sheikh discovered that the toxin suppresses a whole suite of genes related to the lining of the intestines, where nutrients are absorbed. The so-called brush border of the intestine is composed of microscopic, finger-like projections called microvilli that are tightly packed over the surface of the intestines like bristles on a brush. When Fleckenstein and Sheikh applied the toxin to clusters of human intestinal cells, the brush border disintegrated.

“Instead of being nice and tight and upright with thousands of microvilli per cell, they are short, floppy and sparse, kind of like if you had plucked out most of the bristles, and what was left was kind of raggedy,” said Sheikh, who led the 2020 and current studies. “That alone would have a negative impact on the body’s ability to absorb nutrients. But on top of that, we found that genes related to absorbing specific vitamins and minerals -; notably vitamin B1 and zinc -; also were downregulated. That could explain some of the micronutrient deficiencies we see in children repeatedly exposed to these bacteria.”

Children in low- and middle-income countries tend to get diarrhea over and over, and the risk of malnutrition and stunting goes up with each bout. Studying infant mice, the researchers found that a single infection with toxin-producing E. coli was sufficient to damage the brush border, while repeated infections led to extensive intestinal damage and growth lag. Pups infected with a strain of E. coli that lacks the toxin showed no such intestinal damage or stunting.

If the toxin is the problem, an immune response neutralizing the toxin may prevent the long-term effects, Fleckenstein and Sheikh reasoned. To find out, they vaccinated nursing mouse mothers with the toxin. Suckling mice are too young to be immunized themselves, but their vaccinated mothers produce antibodies that pass to the pups through breast milk. The researchers found that the intestines of infant mice from vaccinated mothers appeared healthy, suggesting that vaccination can protect against the intestinal damage leading to malnutrition.

“This is an argument for developing a vaccine for this kind of E. coli,” Fleckenstein said. “There are lifelong consequences of getting infected over and over in childhood. Vaccination combined with efforts to improve sanitation and access to clean water could protect children from the long-term effects and give them a better shot at long and healthy lives.”

Source:

Washington University in St. Louis

Journal reference:

Sheikh A, Tumala B, Vickers TJ, Martin JC, Rosa BA, Sabui S, Basu S, Simoes RD, Mitreva M, Storer C, Tyksen E, Head RD, Beatty W, Said HM, Fleckenstein JM. Enterotoxigenic Escherichia coli heat-labile toxin drives enteropathic changes in small intestinal epithelia. Nature Communications. Nov. 12, 2022. DOI: 10.1038/s41467-022-34687-7

Microbiology

More land is used to grow wheat than any other crop, and wheat is a common cereal that’s …

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More land is used to grow wheat than any other crop, and wheat is a common cereal that’s eaten around the world. Wheat is estimated to provide about 18 percent of the food calories that people around the world need every day. Now researchers are warning that fungi pose a growing threat to wheat, a critical part of our food supply. Nearly half of the wheat crops in Europe are already affected by fungal infections that can generate toxic compounds called mycotoxins, according to new research in Nature Food.

Image credit: Pexels/Pixabay

Fungi can cause a disease called Fusarium Head Blight, which affects cereals. If people or animals eat cereals that are contaminated by mycotoxins, it may cause gastrointestinal issues like vomiting. Mycotoxins also have an economic impact, and lower the value of the crops they contaminate.

Both contaminated crops and Fusarium toxins are a serious concern, and pose a significant threat to our health, in part because we don’t fully understand how they affect our well-being, said study leader and fungal biologist Dr. Neil Brown of the University of Bath.

“But on top of these health concerns, we must remember that wheat is a hugely important global crop, so it’s essential for us to maintain high yields along with safe food production, not least because climate change, and now the war in Ukraine (the world’s fourth largest wheat exporter), are already impacting on wheat yields and grain prices.” It will be important to protect food security and maintain a stable wheat price, Brown added.

The researchers studied data on Fusarium mycotoxins in wheat that has been collected in Europe for the past decade. This showed that mycotoxins are present in wheat in every European country. More than half of the wheat in Europe that is grown for human consumption carries Fusarium mycotoxin, also known as “DON” or vomitoxin. Levels are higher in the U.K., where 70 percent of wheat is contaminated.

There are legal limits on DON levels in wheat that meant to be eaten by humans, and it’s estimated that 95 percent of the wheat that people consume does meet safety standards for DON levels. But the ubiquitous nature of the toxins revealed by this study has suggested that very low levels of mycotoxins might be found in people’s diets, and possibly for a very long time.

“There are real concerns that chronic dietary exposure to these mycotoxins impacts human health,” said Brown.

While there are mycotoxin limits for humans, animals seem to be eating high levels of DON mycotoxin. “It’s far higher than in human food. This is a concern for animal health, but it also paints a picture of what mycotoxin levels in food wheat could look like without current regulations,” noted first study author Louise Johns, a graduate student in the Brown group.

There is also a lot we still don’t know about Fusarium toxins. We don’t know why the levels of these toxins are increasing, although it may have to do with agricultural practices and climate change. We also still have more to learn about how the toxins interact with other chemicals, and how they affect human health.

The researchers noted that surveillance for mycotoxins should increase. Not all wheat is tested regularly, and this study also showed that 25 percent of the DON-contaminated wheat was also carrying other types of mycotoxins.

Sources: University of Bath, Nature Food


Carmen Leitch

Microbiology

Scientists identify molecules in mucus that can block cholera infection

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Reviewed by Emily Henderson, B.Sc.Dec 13 2022

MIT researchers have identified molecules found in mucus that can block cholera infection by interfering with the genes that cause the microbe to switch into a harmful state.

These protective molecules, known as glycans, are a major constituent of mucins, the gel-forming polymers that make up mucus. The MIT team identified a specific type of glycan that can prevent Vibrio cholerae from producing the toxin that usually leads to severe diarrhea.

If these glycans could be delivered to the site of infection, they could help strengthen the mucus barrier and prevent cholera symptoms, which affect up to 4 million people per year. Because glycans disarm bacteria without killing them, they could be an attractive alternative to antibiotics, the researchers say.

Unlike antibiotics, where you can evolve resistance pretty quickly, these glycans don’t actually kill the bacteria. They just seem to shut off gene expression of its virulence toxins, so it’s another way that one could try to treat these infections.”

Benjamin Wang PhD ’21, one of the lead authors of the study

Julie Takagi PhD ’22 is also a lead author of the paper. Katharina Ribbeck, the Andrew and Erna Viterbi Professor of Biological Engineering at MIT, is the senior author of the study, which appears today in the EMBO Journal.

Other key members of the research team are Rachel Hevey, a research associate at the University of Basel; Micheal Tiemeyer, a professor of biochemistry and molecular biology at the University of Georgia; and Fitnat Yildiz, a professor of microbiology and environmental toxicology at the University of California at Santa Cruz.

Taming microbes

In recent years, Ribbeck and others have discovered that mucus, which lines much of the body, plays a key role in controlling microbes. Ribbeck’s lab has showed that glycans -; complex sugar molecules found in mucus -; can disable bacteria such as Pseudomonas aeruginosa, and the yeast Candida albicans, preventing them from causing harmful infections.

Most of Ribbeck’s previous studies have focused on lung pathogens, but in the new study, the researchers turned their attention to a microbe that infects the gastrointestinal tract. Vibrio cholerae, which is often spread through contaminated drinking water, can cause severe diarrhea and dehydration. Vibrio cholerae comes in many strains, and previous research has shown that the microbe becomes pathogenic only when it is infected by a virus called CTX phage.

“That phage carries the genes that encode the cholera toxin, which is really what’s responsible for the symptoms of severe cholera infection,” Wang says.

In order for this “toxigenic conversion” to occur, the CTX phage must bind to a receptor on the surface of the bacteria known as the toxin co-regulated pilus (TCP). Working with mucin glycans purified from the pig gastrointestinal tract, the MIT team found that glycans suppress the bacteria’s ability to produce the TCP receptor, so the CTX phage can no longer infect it.

The researchers also showed that exposure to mucin glycans dramatically alters the expression of many other genes, including those required to produce the cholera toxin. When the bacteria were exposed to these glycans, they produced almost no cholera toxin.

When Vibrio cholerae infects the epithelial cells that line the gastrointestinal tract, the cells begin overproducing a molecule called cyclic AMP. This causes them to secrete massive amounts of water, leading to severe diarrhea. The researchers found that when they exposed human epithelial cells to Vibrio cholerae that had been disarmed by mucin glycans, the cells did not produce cyclic AMP or start leaking water.

Delivering glycans

The researchers then investigated which specific glycans might be acting on Vibrio cholerae. To do that, they worked with Hevey’s lab to create synthetic versions of the most abundant glycans found in the naturally occurring mucin samples they were studying. Most of the glycans they synthesized have structures known as core 1 or core 2, which differ slightly in the number and type of monosaccharides they contain.

The researchers found that core 2 glycans played the biggest role in taming cholera infection. It is estimated that 50 to 60 percent of people infected with Vibrio cholerae are asymptomatic, so the researchers hypothesize that the symptomatic cases may occur when these cholera-blocking mucins are missing.

“Our findings suggest that maybe infections occur when the mucus barrier is compromised and is lacking this particular glycan structure,” Ribbeck says.

She is now working on ways to deliver synthetic mucin glycans, possibly along with antibiotics, to infection sites. Glycans on their own cannot attach to the mucosal linings of the body, so Ribbeck’s lab is exploring the possibility of tethering the glycans to polymers or nanoparticles, to help them adhere to those linings. The researchers plan to begin with lung pathogens, but also hope to apply this approach to intestinal pathogens, including Vibrio cholerae.

“We want to learn how to deliver glycans by themselves, but also in conjunction with antibiotics, where you might need a two-pronged approach. That’s our main goal now because we see so many pathogens are affected by different glycan structures,” Ribbeck says.

The research was funded by the National Institute of Biomedical Imaging and Bioengineering, the Materials Research Science and Engineering Centers Program of the U.S. National Science Foundation, the National Institute of Environmental Health Sciences, a Training Grant in Environmental Toxicology from the MIT Center for Environmental Health Sciences, the National Institutes of Health, and a Swiss National Science Foundation grant.

Source:

Massachusetts Institute of Technology

Journal reference:

Wang, B.X., et al. (2022) Host-derived O-glycans inhibit toxigenic conversion by a virulence-encoding phage in Vibrio cholerae. The EMBO Journal. doi.org/10.15252/embj.2022111562.

Microbiology

Vaccination against E. coli could help prevent some forms of childhood malnutrition, stunting

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Reviewed by Emily Henderson, B.Sc.Dec 7 2022

Diarrhea is no longer the killer it was in the mid-20th century, when an estimated 4.5 million children under age 5 died of it every year. While life-saving oral rehydration therapy turned the tide, it doesn’t prevent infection. Millions of children in low- and middle-income countries still endure repeated bouts of diarrhea that weaken their bodies and leave them vulnerable to malnutrition and stunted growth, and less able to fight off a wide range of infections.

Researchers at Washington University School of Medicine in St. Louis have determined, in studies of human cells as well as mice, how some types of diarrhea-causing Escherichia coli (E. coli) bacteria damage the intestines to cause malnutrition and stunting. And they’ve shown that vaccinating against a toxin produced by E. coli protects infant mice from intestinal damage.

The findings suggest that a vaccine against this kind of E. coli could boost global efforts to ensure that all children not only make it to age 5, but thrive. The study is available online in Nature Communications.

Ideally, we’d like to have a vaccine that prevents acute diarrhea, which still kills half a million children a year, and that also protects against long-term effects such as malnutrition, which is perhaps the bigger part of the problem now. When kids become malnourished, their risk of dying from any cause goes up. The World Health Organization is in the process of deciding how to prioritize vaccines for kids in low- and middle-income countries, and I think these data suggest that vaccinating kids against E. coli diarrhea could be hugely beneficial in places that struggle with this.”

James M. Fleckenstein, MD, senior author, professor of medicine and of molecular microbiology

Fleckenstein studies a kind of E. coli known as enterotoxigenic E. coli, or ETEC -; so named for the two toxins it produces -; and its effects on children who live where the bacteria run rampant. E. coli is a common cause of diarrhea worldwide, but the strains found in the U.S. and other high-income countries typically don’t carry the same toxins as those in low- and middle-income countries. And that may make all the difference.

A 2020 study by Fleckenstein and Alaullah Sheikh, PhD -; then a postdoctoral researcher in Fleckenstein’s lab and now an instructor in medicine -; indicated that one of ETEC’s two toxins, heat-labile toxin, does more than trigger a case of the runs. The toxin also affects gene expression in the gut, ramping up genes that help the bacteria stick to the gut wall.

As part of the latest study, Fleckenstein and Sheikh discovered that the toxin suppresses a whole suite of genes related to the lining of the intestines, where nutrients are absorbed. The so-called brush border of the intestine is composed of microscopic, finger-like projections called microvilli that are tightly packed over the surface of the intestines like bristles on a brush. When Fleckenstein and Sheikh applied the toxin to clusters of human intestinal cells, the brush border disintegrated.

“Instead of being nice and tight and upright with thousands of microvilli per cell, they are short, floppy and sparse, kind of like if you had plucked out most of the bristles, and what was left was kind of raggedy,” said Sheikh, who led the 2020 and current studies. “That alone would have a negative impact on the body’s ability to absorb nutrients. But on top of that, we found that genes related to absorbing specific vitamins and minerals -; notably vitamin B1 and zinc -; also were downregulated. That could explain some of the micronutrient deficiencies we see in children repeatedly exposed to these bacteria.”

Children in low- and middle-income countries tend to get diarrhea over and over, and the risk of malnutrition and stunting goes up with each bout. Studying infant mice, the researchers found that a single infection with toxin-producing E. coli was sufficient to damage the brush border, while repeated infections led to extensive intestinal damage and growth lag. Pups infected with a strain of E. coli that lacks the toxin showed no such intestinal damage or stunting.

If the toxin is the problem, an immune response neutralizing the toxin may prevent the long-term effects, Fleckenstein and Sheikh reasoned. To find out, they vaccinated nursing mouse mothers with the toxin. Suckling mice are too young to be immunized themselves, but their vaccinated mothers produce antibodies that pass to the pups through breast milk. The researchers found that the intestines of infant mice from vaccinated mothers appeared healthy, suggesting that vaccination can protect against the intestinal damage leading to malnutrition.

“This is an argument for developing a vaccine for this kind of E. coli,” Fleckenstein said. “There are lifelong consequences of getting infected over and over in childhood. Vaccination combined with efforts to improve sanitation and access to clean water could protect children from the long-term effects and give them a better shot at long and healthy lives.”

Source:

Washington University School of Medicine

Journal reference:

Sheikh, A., et al. (2022) Enterotoxigenic Escherichia coli heat-labile toxin drives enteropathic changes in small intestinal epithelia. Nature Communications. doi.org/10.1038/s41467-022-34687-7.

Microbiology

Retching Mice Reveal the Brain Circuit Behind Vomiting

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ABOVE: Staphylococcus aureus © ISTOCK.COM, Artur Plawgo

Nausea is a universally unwelcome feeling, but despite such widespread aversion, very little has been learned about the mechanism that causes an organism to vomit. That’s now changed with a report published yesterday in Cell that describes a neural pathway that purportedly controls retching in mice. The finding could lay the foundation for the development of new antinausea drugs, particularly for chemotherapy patients, according to a news release from the journal.

When someone eats food containing certain bacteria, the microbes generate toxins that are detected by the brain. The brain then induces a variety of defensive responses designed to get the toxins out of the body. These include retching and vomiting, the study authors write, as well as feelings of nausea, which they say teaches the host to avoid the contaminated food in the future. Although these toxin responses are typically useful for survival, they are also responsible for a side effect of chemotherapy, they add. According to The New York Times, the nausea caused by chemotherapy drugs can make food unpalatable, resulting in difficulty maintaining weight. Peng Cao, a neuroethologist at Tsinghua University in Beijing and coauthor of the study, says he wanted to figure out what exactly was causing this nausea.

“If we want to get better medications, we need to know the detailed mechanism,” he tells the Times.

Cao and the rest of the team wanted to perform their experiment on mice, but the animals aren’t able to vomit. However, the researchers found that when mice were given staphylococcal enterotoxin A (SEA), a toxin produced by the pathogenic bacteria Staphylococcus aureus, they made facial expressions with wide and contorted mouths, and contracted their abdominal muscles in a similar way to dogs when they are about to vomit. Mice given saline solution as a control did not have the same reaction. The researchers concluded that the mice that ingested SEA were doing something akin to dry heaving or retching, which served as a proxy for vomiting in other animals.

See “T Cells That Drive Toxic Shock in Mice Identified”

Examining mice that had received SEA, the researchers found that the toxin induced the release of the neurotransmitter serotonin. The serotonin activated sensory neurons in the intestine, which sent signals to what is known as the dorsal vagal complex (DVC), a region in the brainstem that is thought to control digestive processes. They found that these signals primarily triggered activity in Tac-1+ neurons; when Cao and the team found a way to inactivate Tac-1+ neurons in the DVC, the mice retched significantly less.

The scientists found that the chemotherapy drug doxorubicin also caused retching, indicating that chemotherapy drugs and bacterial toxins induce similar defensive neural responses. Moreover, when they repeated the inactivation of Tac-1+ neurons before giving mice doxorubicin, the mice once again retched less than those whose neurons were unaltered did after receiving the drug. Knowing this, and better understanding the pathways that lead to nausea and vomiting, could be an important first step in developing better antinausea drugs and improving the quality of life of chemotherapy patients, Cao tells the Times, provided the results are mirrored in humans.

“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,” he says in the journal’s news release.

See “Mopping Up Excess Chemotherapy Drugs”