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World J Gastroenterol. Mar 7, 2008; 14(9): 1399-1405
Published online Mar 7, 2008. doi: 10.3748/wjg.14.1399
Intestinal permeability and its association with the patient and disease characteristics in Crohn’s disease
Jaya Benjamin, Govind K Makharia, Vineet Ahuja, Mani Kalaivani, Yogendra K Joshi
Jaya Benjamin, Govind K Makharia, Vineet Ahuja, Yogendra K Joshi, Department of Gastroenterology & Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India
Mani Kalaivan, Department of Biostatistics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India
Author contributions: Benjamin J designed the study, performed the research and wrote the paper; Joshi YK, chief investigator of the project designed and guided the research work; Makharia GK and Ahuja V provided the patient material and other clinical data; Kalaivani M did the statistical data analysis.
Correspondence to: Professor Yogendra Kumar Joshi, Department of Gastroenterology & Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India. ykj2511@usa.net
Telephone: +91-11-26594290
Fax: +91-11-26588641
Received: October 19, 2007
Revised: December 17, 2007
Published online: March 7, 2008
Abstract

AIM: To assess the intestinal permeability (IP) in patients with Crohn’s disease (CD) and study the association of IP with the patient and disease characteristics.

METHODS: One hundred and twenty five consecutive patients of CD (Males: 66) were diagnosed on the basis of a combination of standard clinical, endoscopic, imaging and histological features. CD activity index (CDAI) was used to calculate the activity of the disease while the behavior of the disease was assessed by the modified Montreal classification. IP was measured by the ratio of the percentage excretion of ingested doses of lactulose and mannitol in urine (LMR). The upper limit of normality of LMR (0.037) was derived from 22 healthy controls.

RESULTS: Thirty six percent of patients with CD had increased IP. There was no significant difference in mannitol excretion (patients vs controls = 12.5% vs 14.2%, P = 0.4652), but lactulose excretion was significantly higher in patients compared to healthy controls (patients vs controls = 0.326% vs 0.293%, P = 0.0391). The mean LMR was also significantly higher in the patients as compared to healthy controls [0.027 (0.0029-0.278) vs 0.0164 (0.0018-0.0548), P = 0.0044]. Male patients had a higher LMR compared to females [0.036 (95% CI 0.029, 0.046) vs 0.022 (95% CI 0.0178, 0.028) (P = 0.0024), though there was no difference in the number of patients with abnormal IP in both the sexes. Patients with an ileo-colonic disease had a higher LMR than those with only colonic disease [0.045 (95% CI 0.033, 0.06) vs 0.021 (95% CI 0.017, 0.025) (P < 0.001)]. Of patients with ileo-colonic disease, 57.8% had an abnormal IP, compared to 26.7% with colonic and 15.6% with small intestinal disease. Patients with a stricturing disease had significantly higher LMR compared to non-fistulising non-stricturing disease [0.043 (95% CI 0.032, 0.058) vs 0.024 (95% CI 0.019, 0.029) (P = 0.0062)]. There was no correlation of IP with age, disease activity, duration of illness, D-xylose absorption, upper GI involvement, perianal disease, and extra-intestinal manifestations. On multiple regression analysis, male gender and ileo-colonic disease were independent factors associated with increased IP. Gender, location, behavior of the disease and upper GI involvement could explain up to 23% of variability in IP (R2 = 0.23).

CONCLUSION: IP was increased in 36% of patients with CD. Male gender and an ileo-colonic disease were the independent factors associated with increased IP.

Keywords: Lactulose mannitol ratio, Crohn’s disease, Inflammatory bowel disease, Intestinal barrier, Crohn’s disease activity index, Intestinal permeability