New research shows that this RNA segment sends signals that stop the activity of the gene that produces glutamine, an amino acid. Previous research has linked a shortage of glutamine in the gut with the seepage of toxins and bacteria through the intestinal wall, irritating nerves and creating disease symptoms.
Scientists say that trying to generate glutamine in the disordered bowel by silencing this RNA segment could open up a whole new way of thinking about treating the diarrhea-predominant type of irritable bowel syndrome (IBS). In the meantime, they are making plans to conduct a clinical trial to see if glutamine supplements could also reduce common IBS symptoms.
In the Ohio State University study, researchers observed that in human tissue samples, the presence of this small piece of RNA was associated with reduced activity by the gene that produces glutamine. Lower levels of glutamine were seen only in tissue samples from patients with the diarrhea-predominant type of IBS.
A group of these patients also had a condition called increased intestinal permeability, which allows toxins and bacteria into the colon that typically can’t get in. The resulting irritation to nerves in the colon is believed to contribute to diarrhea and abdominal pain. The finding suggests that the glutamine deficiency is connected to the increased intestinal permeability, which dramatically increases the likelihood that diarrhea-predominant IBS symptoms will follow.
The researchers say that manipulating that tiny piece of RNA, known as microRNA-29a, has potential as a novel treatment for IBS. “We’ve known about characteristics of this disease, but we didn’t know the reasons behind them. This study helps us connect everything together. Maybe if we can modulate the microRNA, we can heal the disease. That is our whole hypothesis,” said QiQi Zhou, assistant professor of internal medicine at Ohio State and lead author of the study.
The research is published in a recent issue of the journal Gut.
“We treat the disorder, but we still don’t understand it completely,” said study senior co-author G. Nicholas Verne, professor of internal medicine and director of the Division of Gastroenterology, Hepatology and Nutrition at Ohio State. “We often have to use multiple therapies to attack the symptoms, but the pain is by far the most difficult to treat. For some patients, the pain responds only to escalating doses of narcotics or tricyclic antidepressants.
This work was supported by the National Institutes of Health and the Medical Research Service of the Department of Veterans Affairs.
Co-authors, both from Ohio State, include Wiley Souba, dean of the College of Medicine; and Carlo Croce, professor and chair of the Department of Molecular Virology, Immunology and Medical Genetics. Verne and Zhou also are affiliated with the Cincinnati VA Medical Center Research Service.