Background: Controversy surrounds the issue of intestinal permeability in patients with coeliac disease, polyethylene glycol 400 indicating reduced and di-/mono-saccharide urine excretion ratios and Cr-51-labeled ethylenediaminetetraacetic acid (EDTA) indicating increased permeability. Methods: We assessed the suitability of polyethylene glycol 400, L-rhamnose, lactulose, and Cr-51-EDTA as markers of intestinal permeability by assessing urine excretions after simultaneous intravenous instillation of these markers and after oral administration in normals and patients with coeliac disease. Results: After intravenous administration the 24-h urine excretion of polyethylene glycol 400, L-rhamnose, lactulose, and Cr-51-EDTA was 40%, 72%, 93%, and 97%, respectively. There was no significant difference between controls and patients with coeliac disease. Oral administration of the markers in an iso- and hyper-osmolar test solution demonstrates reduced permeation due to an osmotic retention effect of lactulose. In contrast, hyperosmolar glycerol increases permeation of all markers except L-rhamnose. Timing of urines and altering osmolarity is important for the behaviour of individual markers but does not enhance the discrimination between controls and patients when the differential urine excretion of lactulose/L-rhamnose is used. The sensitivity of the urine excretion ratio of lactulose/L-rhamnose was comparable to that of Cr-51-EDTA used by itself. Whereas lactulose/L-rhamnose and Cr-51-EDTA showed increased intestinal permeability in coeliac disease, the permeation of polyethylene glycol was reduced. Permeation of the markers did not correlate significantly with jejunal histology. Conclusions: Correlations of marker permeation rates with test dose osmolarity in controls and patients with coeliac disease shows a variable lack of conformity, suggesting that the markers may permeate the intestine by different routes, which are affected to a different extent in coeliac disease.
