Why Does Inflammatory Bowel Disease Keep Relapsing? Scientists Find a New Clue in the Intestinal Wall

For patients with inflammatory bowel disease, improvement of symptoms after treatment does not necessarily mean lasting recovery; the disease may relapse after some time.

For those with inflammatory bowel disease, improvement in symptoms after treatment does not necessarily mean permanent recovery, and the disease may recur after some time.

According to the selection report and quoted by ScienceAlert; The results of a new study show that part of the cause of these frequent relapses may be related to intestinal cells; Cells that remain vulnerable even after symptoms such as abdominal pain and diarrhea are controlled.

Crohn's disease and ulcerative colitis are the two main forms of inflammatory bowel disease (IBD). Both diseases are associated with chronic inflammation of the digestive system.

Treatment can bring the disease to the stage of recovery or subside the symptoms; The stage in which the activity of the disease decreases. However, this situation is not always stable and the inflammation may intensify again.

Crohn's disease is an inflammatory bowel disease that can affect different parts of the intestinal wall. In this disease, the inflamed parts may be located among parts of the intestine that appear healthy.

Researchers found signs of abnormal cell death in the intestinal tissue of some patients, even those whose disease was under control.

"There may still be vulnerabilities in the gut that are not detectable just by looking at the patient's symptoms," said gastroenterologist Britt Christensen.

This study, published in the scientific journal Science, examined more than 900 intestinal tissue samples from 80 people with and without inflammatory bowel disease. Most of the affected patients had inactive or mildly active disease.

This research was conducted under the supervision of researchers from the Walter and Eliza Hall Institute in Australia and focused on the inner lining of the intestine; A protective layer whose cells are constantly replaced and regenerated.

Under normal conditions, controlled cell death helps remove damaged or unnecessary cells, and stem cells make new cells to replace them.

But the researchers found that inflammation can change the behavior of intestinal cells, making them more vulnerable to messages that trigger abnormal cell death.

Some of these cellular messages were detected even in tissues that did not have obvious signs of inflammation. This finding suggests that cellular problems may persist beneath the apparently healthy surface.

"This finding suggests that the resolution of clinical symptoms does not necessarily mean that the body's underlying biological processes have returned to normal," Christensen explained.

Two different pathways for intestinal cell death

To investigate these processes more closely, the researchers used human samples to grow small and miniature intestinal tissues in the laboratory. These laboratory models, called "organoids," allow scientists to study the response of cells to inflammation.

In the experiments, an unexpected connection between the two types of cell death was revealed.

Examining the tissues of the patients showed signs of a process called "necroptosis". In this process, the cells may rupture and release their contents; An event that can exacerbate inflammation.

But when the researchers exposed the intestinal organoids to inflammatory messages, the cells died mainly through another process called apoptosis. Apoptosis is a type of programmed cell death in which the cell breaks down in an orderly fashion.

The researchers also found that blocking the necroptosis pathway did not prevent cell death under the conditions tested. This suggests that drugs that target only one of the messages identified in the patient's tissue may not alone be sufficient to protect intestinal cells.

In the laboratory, removing certain genes was able to protect certain types of cells. However, more research is needed to determine whether these mechanisms can be safely targeted in patients.

Can this discovery predict the recurrence of the disease?

The researchers further investigated whether the findings related to the intestinal tissue could be related to subsequent recurrences of the disease or not.

Among 52 patients with inflammatory bowel disease, follow-up information was available for 30 patients during a period of two to three years. During this period, the disease of 16 people became active again and they needed to change or intensify the treatment; While the condition of 14 other people remained stable. The follow-up information of 22 patients was not available.

The results showed that patients who later relapsed had a higher level of one of the markers associated with cell death signaling, compared to people without inflammatory bowel disease.

However, this comparison alone does not prove that this marker can determine which patients will relapse in the future.

Also, patients whose disease relapsed had more microscopic inflammation at the beginning of the study; Inflammation that is detected by examining the tissue under a microscope, even if there are no obvious symptoms.

More extensive research could determine whether examining these cellular messages, beyond routine measurements of inflammation, provides clinicians with useful information about the likelihood of disease recurrence.

Christensen cautioned that patient follow-up results are promising, but still preliminary.

The next goal: actual recovery of intestinal tissue

According to the researchers, these findings can now help explain why inflammatory bowel disease relapses after a period of remission; But still these markers cannot be used as a test to predict disease recurrence in patients.

"Therefore, protecting the lining of the gut and maintaining its ability to regenerate, along with treatments that control inflammation, can help patients improve," Christensen said.

Of course, cell death pathways have important functions in the body and help remove damaged cells or cells that may become cancerous. For this reason, curbing these routes without carefully examining possible risks can have unwanted consequences.

"We have not yet shown that blocking these mechanisms can safely prevent relapse in patients," Christensen emphasized.

The researchers' long-term goal is to achieve what Christensen calls "molecular repair"; It means identifying and eliminating cellular disorders that remain even after the patient's appearance improves.

However, it remains to be seen whether correcting these disorders can help patients live longer without relapse.