Impaired intestinal permeability linked to bowel symptoms in IBD

Last Updated: 2017-06-22

By Will Boggs MD

NEW YORK (Reuters Health) - Ongoing bowel symptoms can occur as a result of impaired intestinal permeability despite mucosal healing in patients with inflammatory bowel disease (IBD), researchers from Australia report.

As many as 35% of IBD patients remain symptomatic with abdominal pain and altered bowel habits, symptoms that overlap with irritable bowel syndrome (IBS), despite mucosal healing. The origin of these symptoms remains uncertain.

Dr. Rupert W. Leong and colleagues from the University of New South Wales, in Sydney, examined the association of small intestinal permeability, as detected by confocal laser endomicroscopy (CLE), and ongoing symptoms in their prospective study of 86 IBD patients, 49 of whom had achieved mucosal healing, and 22 controls.

Among the 49 IBD patients with mucosal healing, 16.3% had ongoing bowel symptoms (15.4% of those with Crohn's disease and 17.4% of those with ulcerative colitis), the team reports in Gastroenterology, online June 7.

The median Confocal Leak Score (CLS, from 0=no impaired permeability to 100=complete loss of barrier function) was significantly higher in IBD patients with mucosal healing (12.9) than in controls (5.9). And symptomatic IBD patients had significantly higher scores (18.9) than did asymptomatic patients (7.3), with no significant difference between controls and asymptomatic IBD patients.

Results were similar in subgroup analyses of patients with ulcerative colitis and Crohn's disease.

A CLS level of 13.1 or higher defined ongoing bowel symptoms in IBD with a sensitivity of 95.2% and a specificity of 97.6%, with 36.2% of IBD patients in mucosal healing having intestinal permeability about this cutoff level.

On multiple linear regression, CLS increased by 1.87 for each additional daily diarrheal episode.

Among IBD patients with mucosal healing, neither erythrocyte sedimentation rate (ESR) nor C-reactive protein (CRP) differed significantly between those with and without symptoms.

“This study supports the role of impaired intestinal permeability as a contributing factor towards ongoing bowel symptoms despite mucosal healing in IBD,” the researchers conclude. “In addition, it demonstrated the role of CLE as an effective tool in the assessment of intestinal permeability beyond its traditional role of obtaining virtual histology.”

“Longitudinal and interventional studies are likely to be helpful to better understand intestinal barrier dysfunction and its potential for recovery,” they note.

“This supports that the ultimate treatment target of IBD should include not only mucosal healing but also recovery of the intestinal mucosal barrier function,” the researchers add.

Dr. Levinus A. Dieleman from the University of Alberta, in Edmonton, Canada, who has investigated intestinal permeability in a variety of conditions, told Reuters Health by email, “Almost all clinical trials with new agents for IBD require mucosal healing as one of their end-points. This is an important parameter, as mucosal healing correlates with a better natural course of disease and complications, less steroid usage, and less hospitalizations and emergency room visits. This manuscript shows that there is another therapeutic target that is even ‘deeper’ than endoscopic and microscopic healing.”

“The authors show that a leaky gut in a non-involved area, such as the normal terminal ileum, is associated with persistent symptoms such as diarrhea,” he said.

“At this time, confocal microscopy is performed almost solely in academic centers and does not seem practical for the community gastroenterologist,” Dr. Dieleman added. “However, since novel therapeutic agents for IBD are tested at these centers, the addition of CLE will be required to also assess intestinal permeability as a novel endpoint of such trials.”

“My group recently described in the online Clinical Gastroenterology and Hepatology that a quarter of asymptomatic first-degree relatives of patients with Crohn’s disease have an intrinsic abnormal gut permeability, and that this was not associated with early Crohn’s lesions, as assessed by video capsule,” Dr. Dieleman said. “A lot of research is being done in what factors play a role in such ‘leaky gut barrier’ with detailed study of the intestinal barrier. It has been shown that, e.g., the gut bacteria can alter this barrier, opening the door for adjunct therapies with probiotics, dietary fibers, or diets.”

“Agents that induce mucosal healing and also improve the leaky gut barrier with symptom control will likely become the best therapies for IBD patients, as patients require not only mucosal healing but also control of their symptoms, such as diarrhea,” he concluded.

Dr. Leong did not respond to a request for comments.

SOURCE: http://bit.ly/2sYeJ5h

Gastroenterology 2017.