The levels of a molecule named microRNA-31 may serve as indicators of disease severity and progression in adults and children with Crohn’s disease (CD).
“For such a clinically heterogenous [with diverse presentations] disease, this kind of molecular phenotyping [marking] is a major step towards personalization of medical therapy,” Shehzad Z. Sheikh, MD, PhD, co-author of the paper and associate professor of medicine and genetics at UNC School of Medicine said in a press release.
The study, “Colonic epithelial miR-31 associates with the development of Crohn’s phenotypes,” was published in the Journal of Clinical Investigation Insights.
The progression of CD, a chronic inflammatory condition of the gastrointestinal tract, varies from patient to patient, making it challenging to manage the disease.
In this study, researchers used advanced molecular techniques to identify and validate biomarkers that could be used for the prognosis of CD.
Short, non-encoding RNA sequences, called micro RNA (miR), are play a key role in epithelial cell (cells that line organs’ surfaces) biology. Here, the researchers evaluated the association of one miR — the miR-31 — with CD intestinal inflammation.
Colon tissues, epithelial cells and immune cells obtained from 18 adults with CD, and 12 controls with no history of inflammatory bowel disease, were analyzed.
They also obtained samples from 76 pediatric CD patients who did not receive any treatment, and compared that data with 51 controls.
To preserve the integrity of the colon tissues and their molecular fingerprint, the teams generated “mini-guts,” or colonoids, that mimic the human intestine and colon using the tissue obtained from patients.
“This innovative system can serve as a personalized testing platform to screen therapeutic agents before administering them to the patient,” Sheikh added.
Researchers found that patients with a low level of miR-31 levels, as detected before surgery, had higher chances of late re-occurrence and worsening of the disease and required surgical intervention to provide an alternate opening for the lower part of the small intestine (ileostomy).
The team also found that children who had low levels of miR-31 at the time of diagnosis later developed complications, such as narrowing of the intestine, which required surgery.
The tissue-preserving technique used in the study played a critical role in obtaining reliable data on miR-31 expression.
“Preserving tissue in this way usually results in heavily degraded mRNA. But our ability to accurately detect microRNA expression that was not degraded in fixed samples opens up future studies to a wealth of patient samples from across the country to further validate microRNA-31 and a suite of other microRNAs as prognostic markers of Crohn’s disease,” said Benjamin P. Keith, graduate student at UNC, School of Medicine and first author of the study.
“These findings represent an important step forward in designing more effective clinical trials and developing personalized CD therapies,” the researchers wrote.
“We are excited about our findings because, while it is just the beginning and more work remains to be done, it opens the possibility of using microRNAs to improve clinical trial designs for Crohn’s disease and developing more personalized therapeutic strategies for patients,” said Praveen Sethupathy, PhD, current associate professor at Cornell University and the corresponding author of the paper.