Different intestinal permeability patterns in relatives and spouses of patients with Crohn’s disease: an inherited defect in mucosal defence?

Abstract

Background-A familial defect in intestinal barrier function has been found in Crohn's disease. Aim-To investigate possible genetic and environmental influences on this barrier defect by studying intestinal permeability in both relatives and spouses of patients with Crohn's disease. Subjects-The study included 39 patients with Crohn's disease, 34 healthy first degree relatives, and 22 spouses. Twenty nine healthy volunteers served as controls. Methods-Intestinal permeability was assessed as the lactulose:mannitol ratio in five hour urinary excretion after oral load, both before (baseline) and after ingestion of acetylsalicylic acid. The permeability response represents the diVerence between the two tests. A ratio above the 95th percentile for controls was classified as abnormal. Results-Baseline permeability was higher in patients and spouses than in controls. An abnormal baseline permeability was seen in 36% of the patients, 23% of the spouses, 18% of the relatives, and 3% of the controls. After ingestion of acetylsalicylic acid, permeability increased significantly in all groups. Relatives were similar to patients with regard to permeability after exposure to acetylsalicylic acid, whereas spouses were similar to controls. The proportions with an abnormal permeability response to acetylsalicylic acid were 32% in patients, 14% in spouses, 41% in relatives, and 3% in controls. Conclusion-The findings suggest that baseline permeability is determined by environmental factors, whereas permeability provoked by acetylsalicylic acid is a function of the genetically determined state of the mucosal barrier, and support the notion that environmental and hereditary factors interact in the pathogenesis of Crohn's disease. (Gut 1999;44:96-100)

Intestinal permeability and its association with the patient and disease characteristics in Crohn’s disease

“…Similar findings have been shown by Soderholm et al [23] . While Munkholm [32] and Jogerson et al [21] found a negative correlation of age with the absorption of mannitol and excretion of 51 CrEDTA, respectively.…”

“…Jorgensen et al reported an association between the male gender and increased permeation of 14 C-mannitol [21] . On the contrary, Soderholm et al [23] did not find any correlation between IP and gender of the patients with CD. The reason of higher IP in male patients is not clear.…”

“…However, there was no correlation of IP with age, duration, activity of the disease and D-xylose absorption. Thirty three to 68% patients with CD have been reported to have increased IP using a variety of marker probes such as polyethylene glycol (PEG) 400, PEG 1000, 51 CrEDTA, 99m TcDTPA, 51 CrEDTA/ 14 C-mannitol, lactulose, mannitol, rhamnose and cellobiose [21][22][23][24] . In this study, we used lactulose and mannitol (L/M) excretion to quantify IP.…”

Crohn’s disease specific pancreatic antibodies: clinical and pathophysiological challenges

“…Currently, they are believed to be triggered and/or perpetuated by an increased leakiness of the epithelial barrier, disturbance of innate epithelial immune mechanisms, and disturbance of antigen recognition as well as processing of professional and atypical antigen-presenting cells [80][81][82]. Noteworthy, a disturbed regulatory and effector T cell balance appears also to be involved [83,84].…”

Mast cells regulate homeostatic intestinal epithelial migration and barrier function by a chymase/Mcpt4-dependent mechanism

“…While altered intestinal barrier function (increased intestinal epithelial permeability) can be a consequence of disease exacerbation, clinical evidence suggests it may also be a primary etiologic factor predisposing to disease development. For example, increased intestinal permeability is found not only in patients with IBD, celiac disease, and type I diabetes, but also their healthy first-degree relatives (3)(4)(5)(6)(7).…”