Norovirus connection to Crohn’s disease may suggest novel treatments

Norovirus connection to Crohn's disease may suggest novel treatments
Norovirus connection to Crohn's disease may suggest novel treatments

Norovirus connection to Crohn’s disease may suggest novel treatments

A recent study may have shed light on the riddle of Crohn’s disease, an inflammatory bowel disorder in which the body’s own digestive tract is wrongly targeted by immune defenses intended to battle invading microorganisms. One of the viruses and bacteria known to induce illness initiation in Crohn’s patients is the norovirus, a common infection that produces vomiting and diarrhea, although researchers do not yet understand why.

One hint came from earlier research that showed the majority of people with the illness have a certain genetic alteration (mutation). The cells that line the intestines are more prone to injury because of this mutation. However, when it was discovered that half of all Americans have the same genetic mutation that increases risk but that fewer than 500,000 of them go on to acquire Crohn’s disease, the puzzle only grew more enigmatic.

The new research was published online on October 5 in the journal Nature. It demonstrated for the first time that in healthy people, immune defense cells called T cells secrete a protein called apoptosis inhibitor five (API5), which instructs the immune system to stop attacking cells in the gut lining. Due to the extra layer of defence provided by this protein against immune system deterioration, even those with the mutation can maintain a healthy gut. In mice designed to develop a rodent type of Crohn’s disease, the researchers also discovered that norovirus infection limits T cell release of API5, destroying gut-lining cells in the process.

Norovirus connection to Crohn's disease may suggest novel treatments

The study, led by experts from NYU Grossman School of Medicine, provides evidence in favour of the hypothesis that the API5 mutation shields the majority of those with it from disease until a secondary trigger, such norovirus infection, pushes some individuals over the sickness threshold.

In studies using genetically altered mice carrying the mutation associated to Crohn’s disease in humans, mice that received an injection of API5 lived longer than mice in the untreated group by a factor of two. According to the study’s authors, this supported the hypothesis that the protein shields gastrointestinal cells. In human tissue, the researchers discovered that patients with Crohn’s disease had five to 10 times less API5-producing T cells than those without the condition.

According to research lead author and gastroenterologist Yu Matsuzawa-Ishimoto, MD, Ph.D., “Our findings offer new insight into the crucial role that apoptosis inhibitor five plays in Crohn’s disease.” This chemical might offer a fresh approach to combating the long-term management challenges presented by this chronic autoimmune disease.

A postdoctoral research fellow at NYU Langone Health named Matsuzawa-Ishimoto points out that current treatments, which suppress the immune system, put patients at a significant risk for infection and frequently lose their effectiveness after a few years of use. He continues by saying that a therapy that targets API5 might prevent those problems.

In a different series of studies, the researchers used tissue taken from people who had the mutation to build organ-like structures. Notably, only the cells of the gut lining made up these structures. After injecting API5 into these “mini guts,” the study team discovered that this treatment protected the gut-lining cells. T cells that produce API5 were also added, and they protected the gut lining.

According to study co-senior author and biochemist Shohei Koide, Ph.D., “the findings of our investigation assist explain why the genetic linkages to Crohn’s are far wider than the actual number of persons who have the disease.” Koide is a professor in the NYU Langone Perlmutter Cancer Center’s Department of Biochemistry and Molecular Pharmacology.

According to study co-senior author and microbiologist Ken Cadwell, Ph.D., the Recanati Family Professor of Microbiology at NYU Langone, “our study suggests that when norovirus infects those with a weak ability to produce apoptosis inhibitor five, it tips the scales toward a full-blown autoimmune disease.”

Although the study’s authors obtained the API5 protein from human tissue rather than rodents, Cadwell warns that it is yet unknown whether the injection treatment can be used on people without causing harm.

To determine whether the potential medication can successfully manage Crohn’s disease, which can flare up again over time, the research team will next investigate the long-term consequences of API5 injections.

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