Crohn's disease can be triggered by norovirus infection in people with certain genetic mutations

Crohn’s disease can be triggered by norovirus infection in people with certain genetic mutations

Scientists may have found a culprit for what can trigger Crohn’s disease.

In some people, exposure to the highly contagious norovirus could increase the risk of intestinal disorders, which causes the immune system to attack the digestive tract, according to a study published Wednesday in Nature.

Scientists haven’t found exactly what causes the autoimmune disease, although it has been linked to people with certain genetic mutations. Previous research has pointed to a genetic mutation that most people with Crohn’s disease share. However, nearly half of all Americans have this mutation, while only about half a million people in the United States have developed Crohn’s disease, suggesting that a genetic variant isn’t the only cause. .

Using a mouse and tissue model of the human digestive tract, NYU Grossman School of Medicine researchers found that a common norovirus infection may play a role in the disease by blocking the production of a protein called inhibitor of apoptosis five, or API5. This protein – which is released by certain T cells – normally protects intestinal cells by telling the immune system to stop its attacks once a microbe has been defeated.

Norovirus is a highly contagious insect that causes diarrhea and vomiting. Up to 21 million people in the United States become ill with norovirus each year.Charles D. Humphrey/CDC

“What we found is really interesting,” said study co-author Ken Cadwell, a Recanati family professor of microbiology at NYU Grossman School of Medicine in New York City. “Unexpectedly, T cells protect the gut lining, and infectious triggers interfere with this ability.”

People with Crohn’s disease suffer from chronic diarrhea, abdominal pain and weight loss. There is no cure and existing treatments can cause serious side effects. The hope is that the protein API5, or something like it, may hold the key to a possible treatment for Crohn’s disease that won’t weaken the immune system, as many current therapies do.

Cadwell and his colleagues discovered the link between norovirus and Crohn’s disease by accident when they were studying mice that had been engineered to develop the bowel disease. Many of the mice had caught the norovirus, and “the mice only developed intestinal abnormalities in the presence of viral infection,” Cadwell explained.

The researchers noticed this because without the norovirus infection, the T cells that secreted API5 continued to protect the lining of the digestive tract.

On a hunch, the researchers treated the mice that had developed the rodent version of Crohn’s disease with the human version of API5 protein. The treated mice all survived, while half of those that did not receive the protein injections died.

Next, Cadwell and his team explored the protein’s impact on the gut tissues of people with the Crohn’s susceptibility gene and also people without the gene. Because the researchers were only looking at the cells lining the intestine – with no T cells around to protect them – the tissue was susceptible to developing damage. When the researchers treated the tissue with API5, the protein was protective again.

The researchers also found that people with Crohn’s disease had fewer API5-producing T cells.

“While that doesn’t tell you it’s due to norovirus or something else, it gives us more confidence that something happened to these patients that looks like norovirus infection in mice,” Cadwell said.

It’s possible that norovirus isn’t the only germ that can trigger Crohn’s disease, and that the particular genetic mutation the researchers were looking at isn’t the only one that can make the intestinal lining vulnerable to the disease, Cadwell said. But it looks like API5 may offer a pathway to better therapy for Crohn’s patients.

The finding is important but more research is needed, said gastroenterologist Dr. Eugene Yen, associate professor of medicine at Northwestern University Feinberg School of Medicine.

“It’s one thing to know what causes the disease and another to find a way to alter its course,” said Yen, who was not involved in the study.

Still, “most of our progress has been made after discoveries of diseases like this,” Yen said. “It’s exciting and I look forward to future research on this topic.”

Dr. Serre-Yu Wong, a gastroenterologist and instructor in the Mount Sinai Health System’s Division of Gastroenterology, agreed that the research was “remarkable”.

“On the one hand, it shows a direct protective effect of these specialized T cells — which we didn’t know much about — that live in the gut,” Wong said.

“I think this is another important step in dissecting how this very complex disease process works,” said Wong, who was not involved in the new research.

Crohn’s treatments can make infections worse

This would be good news for Heather Schlueter, who learned three years ago that her excruciating abdominal pain was due to Crohn’s disease. The doctors prescribed steroids, a chemotherapy drug, and a biologic drug that suppresses the immune system.

“I’m one of the lucky ones,” Schlueter said. “These drugs have worked remarkably well for me. They put me in remission.

But then Schlueter developed melanoma and after surgery to remove the tumor, she was struck with a life-threatening bacterial infection, which she attributes to the immunosuppressive drugs she was taking to manage her Crohn’s disease.

After much research, the 53-year-old Scottsdale, Arizona resident decided to go off the medication and try to keep her disease in remission through diet, meditation and exercise. Schlueter has been fine for 10 months, but her doctor has warned her the disease could come back even stronger, which is why the idea of ​​a new type of drug that doesn’t suppress the immune system has great appeal.

“It offers me hope,” Schlueter said. “There is nothing new or hopeful on the horizon. If there could be something new that’s less toxic, that’s very exciting for me as a patient.

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