A nasty but short-lasting stomach bug may have lingering consequences for an unlucky few. Researchers have found evidence in mice and human cells that norovirus infection can trigger Crohn’s disease in people already genetically predisposed to it. The findings may also help scientists one day find better treatments for the chronic gut condition.
Crohn’s is one of two major types of inflammatory bowel disease. In Crohn’s, this inflammation occurs along the lining of the digestive tract, most commonly in the small intestine. Symptoms can vary widely in severity but often include diarrhea, weight loss, and intense stomach cramps. Sufferers also tend to experience flare-ups of illness, with symptoms reappearing or getting worse. About 3 million Americans are thought to have IBD.
The underlying mechanism behind Crohn’s and IBD is a dysfunctional immune system that attacks the gut. But there are likely multiple, connected causes as to why this dysfunction arises in the first place. There have been several genetic variations associated with developing Crohn’s, for instance. But it’s also suspected that some infections can trigger Crohn’s as well, while other microbes may worsen the illness.
This new study, led by researchers at New York University, tried to examine the interplay of these risk factors. They studied mice bred to have a mutation linked to Crohn’s, as well as cultivated human gut cells from people with Crohn’s. The mice were exposed to norovirus, which is one of the most common causes of foodborne illness in humans. In these mice, the infection led to a greater risk of intestinal damage and the loss of certain cells in the small intestine, called Paneth cells, which help provide the first line of defense against infection. Their loss or dysfunction appears to play a driving role in causing Crohn’s along the small intestine.
The researchers also identified a protein produced by certain T cells known as apoptosis inhibitor five, or API5, that might provide protection against Crohn’s. In their mice, the norovirus infection appeared to damage Paneth cells by inhibiting the secretion of API5 from T cells.
To test this hypothesis further, the team introduced the protein to mice with Crohn’s-like illness, finding that all the treated mice survived while only half of the untreated mice did. They also tested the protein on gut lining cells taken from Crohn’s patients with and without the mutation, finding that it only appeared to have a protective effect on the cells from people with the mutation. Lastly, they found evidence that people with Crohn’s tend to have lower levels of T cells that produce API5.
The findings were published in Nature on Wednesday.
“What we found is really interesting,” study co-author Ken Cadwell, a professor of microbiology at the NYU Grossman School of Medicine, told NBC News. “In an unexpected way, T-cells protect the lining of the gut and infectious triggers interfere with that ability.”
The results don’t prove that norovirus is a smoking gun trigger for Crohn’s, so more research will be needed to validate what Cadwell and his team have found here. It’s likely that other common microbes can trigger Crohn’s in vulnerable people as well. A study last year, for instance, suggested that a common yeast found in the gut can help cause or worsen IBD symptoms, but only when left unchecked by the immune system. And there may be more genetic mutations that can raise the risk of these infections or other factors triggering Crohn’s.
But if Cadwell’s research continues to show that API5 can short-circuit the complicated chain of events that leads to Crohn’s, that might point to more effective or easier-to-tolerate treatments someday. Standard drugs for Crohn’s usually work by weakening or suppressing the immune system, which can increase the risk of infections in general or other serious complications.
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October 07, 2022 at 03:05AM
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A Common Stomach Bug May Help Cause Crohn's Disease, Study Suggests - Gizmodo
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