Oct. 01, 2025
The intestinal barrier helps maintain the balance between the intestinal mucosa and the luminal contents. An impaired intestinal barrier may cause increased intestinal permeability, exposing the mucosa to luminal contents and triggering an immunologic response that includes intestinal inflammation.
In a study published in Inflammatory Bowel Diseases in 2025, Mayo Clinic researchers sought to expand the understanding of the role that intestinal permeability plays in chronic inflammatory GI conditions, including inflammatory bowel disease (IBD). Noting that this information might be an important step in the development of novel approaches to treating IBD, the researchers also wanted to explore the possible correlation between intestinal permeability and persistent symptoms, with or without inflammation.
"The treatment of IBD is focused almost entirely on the suppression of inflammation with diverse medications including corticosteroids, immunosuppressives and monoclonal antibodies," explains Michael Camilleri, M.D., D.Sc. Dr. Camilleri served as the study publication's corresponding author and is a gastroenterologist and researcher at Mayo Clinic in Rochester, Minnesota. "This approach may indeed bring the patient into remission, but unfortunately there is often a recurrence of acute inflammatory bowel disease that can lead to repeated treatment with the same medications or chronic treatment with those medications."
Study methods
Intestinal permeability
Intestinal permeability
The researchers conducted a 24-hour intestinal permeability test. After an overnight fast, participants ingested 100 mg 13C-mannitol and 1,000 mg lactulose. During the 2 to 24 hours that followed, the researchers collected urine samples and measured urinary excretion of 13C-mannitol and lactulose to assess small intestinal (SI) and colonic (COL) permeability.
The researchers' primary aim was to measure and compare small intestinal (SI) and colonic (COL) permeability in a group of patients with IBD and a group of healthy volunteers (HVs) without IBD. They also sought to compare permeability in patients with active IBD and patients in remission, and they compared each of these groups with the HV control group.
The researchers identified 37 Mayo Clinic patients with IBD, including 17 with Crohn's disease (CD) and 20 with ulcerative colitis (UC), and 37 HVs. Participants with IBD had their levels of disease activity assessed using the Simple Endoscopic Score for CD (SES-CD) and Mayo endoscopy score for UC. Among the 17 patients with CD, seven had active disease (SES-CD above 6), and 10 were in remission (SES-CD 0 to 2). Among the 20 patients with UC, 10 had active disease (Mayo score 2 to 3), and 10 were in remission (Mayo score 0 to 1).
The researchers conducted a 24-hour intestinal permeability test. After an overnight fast, participants ingested 100 mg 13C-mannitol and 1,000 mg lactulose. During the 2 to 24 hours that followed, the researchers collected urine samples and measured urinary excretion of 13C-mannitol and lactulose to assess SI and COL permeability.
Results
Overall, the researchers found that study participants with IBD had higher levels of urinary excretions during the 2- to 24-hour period compared with HV participants.
- The 2- to 24-hour urinary mass excretion of 13C-mannitol was significantly higher among all participants with IBD, both in the active disease (19.7) and remission (18.4) groups, compared with participants in the HV group (13.8).
- The 2- to 24-hour urinary mass excretion of lactulose was significantly higher among all participants with IBD, both in the active disease (3.5) and remission (3.6) groups, compared with participants in the HV group (1.8).
- The were no statistically significant differences in the lactose to 13C-mannitol ratio at 2 to 24 hours (or 2 to 8 and 8 to 24 hours) among participants in the active disease, remission and HV groups.
According to Dr. Camilleri, these findings provide evidence that a marked increase in intestinal or colonic permeability is present among patients with IBD, even among those who are in remission determined by optimal standards such as blood, stool and endoscopic evaluations.
"In fact, this abnormality or increase in permeability among patients in remission was not significantly different from the evidence of impaired barrier function that was observed in patients who had active disease," says Dr. Camilleri. "These increases were significantly different from the values in healthy controls."
Dr. Camilleri and co-authors are hopeful that these observations could point researchers in a new direction when developing novel treatments for IBD.
"The data suggest that future treatments aimed at correcting the impaired barrier function may constitute new approaches that may prevent the recurrence or exacerbations of inflammatory bowel disease," says Dr. Camilleri. "While no medications are currently available, there is also evidence that certain nutrients may be beneficial in restoring normal barrier function, including supplementation of zinc, calcium, anthocyanins, glutamine and other amino acids that are present in bone broth."
Dr. Camilleri notes that additional, larger studies and research to identify dietary, nutritional and pharmacological agents that restore normal barrier function in patients with IBD may further advance knowledge about this issue and improve patient outcomes.
"The opportunity to restore normal barrier function may be very relevant to the prevention of recurrence or exacerbation of inflammatory bowel diseases," says Dr. Camilleri.
For more information
Dunleavy KA, et al. Intestinal permeability in vivo in patients with inflammatory bowel disease: Comparison of active disease and remission. Inflammatory Bowel Diseases. In press.
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