Altered intestinal permeability is predictive of early relapse in children with steroid‐responsive ulcerative colitis

Abstract

SUMMARY AimTo determine if small bowel involvement at diagnosis could predict early relapse in children with ulcerative colitis. MethodsChildren with newly diagnosed ulcerative colitis were evaluated prospectively at three time points: within 1 month, 6 months and 1 year after diagnosis. Clinical activity indices were used to measure disease activity. Laboratory studies were performed at each visit and ⁄ or at the time of relapse. At diagnosis, all patients underwent colonoscopy and a cellobiose ⁄ mannitol small intestinal permeability study. Some children were further investigated with an upper gastrointestinal endoscopy. ResultsThirty-three patients completed the 1-year study. Overall, nine patients (27.3%) relapsed within 6 months of diagnosis, one patient (3%) within 1 year, whereas 23 patients (69.7%) did not relapse. The mean clinical activity indices, laboratory parameters, extent of colonic involvement, upper and lower gastrointestinal histological features were not predictive of early relapse. Results of the cellobiose ⁄ mannitol small intestinal permeability study were significantly higher in children who relapsed within 6 months compared with children who did not relapse (P < 0.013). The cellobiose ⁄ mannitol small intestinal permeability study was abnormal in 77.8% of early relapsers compared with only 8.3% of non-relapsers. ConclusionAbnormal small intestinal permeability in children with ulcerative colitis could predict a more relapsing disease.

The serine protease-mediated increase in intestinal epithelial barrier function is dependent on occludin and requires an intact tight junction

“…The inflammatory bowel diseases (IBD), Crohn's Disease (CD) and ulcerative colitis (UC), are chronic, relapsing diseases of the gastrointestinal tract, and are associated with changes in barrier function. During active inflammation, patients with IBD display increased permeability of the GI tract, and a reduction in barrier function has been shown to predict disease relapse (43,68). First-degree relatives of patients with CD also display increased intestinal permeability (5,14,22,60), which suggests a genetic component to the changes in barrier function.…”

Intestinal Epithelial Barrier Dysfunction in Disease and Possible Therapeutical Interventions

“…Decreased intestinal permeability was predictive of induction of remission in active CD with corticosteroid medication, and inversely, patients who subsequently relapsed displayed increased intestinal permeability [23]. Small intestinal permeability could also predict a more relapsing disease in children with UC [24]. IBD relapse was associated with a reduction of claudin-3 immunostaining at the colonic TJs and concomitant increased claudin-3 urine levels [25].…”

Function of the intestinal epithelium and its dysregulation in inflammatory bowel disease

“…42 Defects in these intercellular junctions have been shown to lead to increased epithelial permeability, which has been reported in those suffering from IBD and firstdegree relatives. [43][44][45][46] Intestinal permeability has also been shown to predict and possibly cause relapse 47,48 and is increased in those at high risk of CD at baseline. 49 Defects in E-cadherin have been of particular interest in IBD research with upregulation in areas of active inflammation 50 and downregulation by pathogens implicated in the development of colitis such as invasive E. coli.…”