Intestinal permeability in children with Crohn's disease and coeliac disease.

Abstract

Mannitol and lactulose were used as probe molecules to measure intestinal permeability in children with active small-bowel Crohn's disease and with untreated coeliac disease. Mannitol and lactulose were administered by mouth in a moderately hypertonic solution (580 mmol (mosmol)/l), and results were expressed as the ratio of the molecules excreted in urine over five hours. Patients with Crohn's disease had a sixfold increase in permeability (due to increased lactulose permeability) and those with coeliac disease a fivefold increase (due to decreased mannitol permeability).From these results the test offers potential as a noninvasive investigation in children with small-bowel disease. IntroductionHydrophilic molecules permeate the healthy small-bowel mucosa at rates which depend on their molecular size.1 2 In clinical practice various non-metabolised sugars used to study adult populations indicate that in villous atrophy there is a decreased absorption of small molecules and an increased absorption of larger molecules.3 Other studies show that the small-bowel mucosa is more permeable to large molecules in patients with eczema and food allergy5 and also during the neonatal period.6 We were interested in this technique as a non-invasive investigation for children and have evaluated two probe molecules, mannitol and lactulose, to measure intestinal permeability in normal subjects and in two differing conditions of abnormal small-bowel mucosa-untreated coeliac disease and active Crohn's disease.

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

“…Therefore, an abnormal LMR was due to higher excretion of lactulose in the urine than a reduced excretion of mannitol. Pearson et al [15] , Murphy et al [3] , Wyatt et al [7] , and Katz et al [27] have also reported similar findings. The probes used to measure IP are water soluble, which cannot penetrate the lipid cell membrane of enterocytes and thus use the paracellular route through the tight junctions (TJs) for per meation.…”

“…Quantitation of these probes in a timed urine collection provides a measure of the fraction of the ingested dose that penetrated the mucosal barrier [14] . The individual variations due to non-mucosal factors (gastric emptying, intestinal transit, dilution by secretions, renal clearance and incomplete urine recovery) are circumvented when the urinary recovery is expressed as a ratio, since both the sugars are equally affected by these factors except the route of permeation [1,15] . A few studies have reported the association of IP with activity and location of Crohn's disease; however, there is a lack of literature on the association of IP with the disease characteristics (duration, extent, behavior, extra-intestinal manifestations) and patient characteristics (age and gender).…”

Measurement of intestinal permeability using mannitol and lactulose in children with diarrheal diseases

“…It is clear that the measurement of intestinal permeability based on the quantified absorption of two sugars of different sizes provides more information and shows higher sensitivity in gastrointestinal disorders than trials which use single sugars for the tests (2,7). Mannitol and lactulose are preferred sugars because of their properties and their hydrophilic and lipophobic characteristics.…”

Is folate absorption impaired by high dose methotrexate?

“…(Taminiau, 1980) and pre-bone marrow transplant chemotherapy also increased intestinal permeability (Gomes et al, 1982). It has been postulated that such changes are due to damage to mucosal junctional complexes and an increase in the villos tip extrusion zone (Pearson et al, 1982). It is possible that the dilated intercellular spaces that were described after low dose MTX were due to increased water entry by this paracellular pathway (Guavava et al, 1981).…”