Intestinal permeability tied to subsequent Crohn's disease risk

Last Updated: 2020-08-26

By Reuters Staff

NEW YORK (Reuters Health) - Increased intestinal permeability is associated with a higher risk of developing Crohn's disease, according to new findings.

Increased intestinal permeability, as measured by the urinary fractional excretion of lactulose to mannitol ratio (LMR), is more prevalent in patients with established Crohn's disease than in healthy individuals, but it has been unclear whether this gut barrier dysfunction precedes the development of Crohn's disease.

Dr. Kenneth Croitoru of Mount Sinai Hospital, in Toronto, Canada, and colleagues used data from 1,420 asymptomatic first-degree relatives of Crohn's disease patients to investigate whether increased intestinal permeability is associated with the future risk of developing Crohn's disease.

Among these individuals, 50 went on to develop Crohn's disease during the study period, while the remaining 1,370 remained asymptomatic.

Abnormal LMR was defined according to two thresholds, a stringent threshold of LMR >0.03 and a more permissive threshold of >0.025. At recruitment, 11.6% of these individuals exceeded the stringent threshold and 19.3% exceeded the permissive threshold.

Baseline LMR measures were significantly higher among individuals who later developed Crohn's disease than among individuals who remained asymptomatic.

After adjustment for age, sex, and family cluster, an increased LMR at recruitment was associated with a significant 92% increase in the risk of developing Crohn's disease, the researchers report in Gastroenterology.

The risk increase was higher when using the stringent threshold (3.03-fold increased risk) than when using the permissive threshold (2.12-fold increased risk).

Increased LMR was significantly associated with disease onset whether the follow-up duration was within or beyond three years of recruitment, although the risk of developing Crohn's disease was much higher when LMR was measured less than three years before diagnosis than when measured earlier.

Individuals with an LMR higher than 0.035 were at increased risk of developing Crohn's disease even after adjustment for fecal calprotectin levels >100 ug/g.

"This prospective study is the first to demonstrate that abnormal intestinal permeability is a significant pre-disease risk factor of Crohn's disease (CD) onset that precedes more than three years prior to disease development," the authors conclude.

"There are currently no available therapies to directly target and restore the intestinal barrier approved by the (U.S. Food and Drug Administration) for this purpose," they note. "Our results suggest that studies are required to discover new drugs to potentially prevent disease onset by promoting and maintaining a healthy gut barrier, especially considering that CD affects over 800,000 individuals in North America and 1.6 million individuals in Europe, along with increasing numbers in many areas of the world."

"The absence of a cure for CD emphasizes the importance of this study, since the identification of early preclinical markers of disease could lead us toward prevention strategies," the researchers add.

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

SOURCE: https://bit.ly/3iXfjGs Gastroenterology, online August 10, 2020.