GASTROENTEROLOGY 1997;112:1129 – 1136 Gastrointestinal Permeability in Celiac Disease EDGARDO SMECUOL,* JULIO C. BAI,* HORACIO VAZQUEZ,* ZULEMA KOGAN, ‡ ANA CABANNE, ‡ SONIA NIVELONI,* SILVIA PEDREIRA,* LUIS BOERR,* EDUARDO MAURIN ˜ O,* and JON B. MEDDINGS § *Department of Gastroenterology, Salvador University, Buenos Aires, Argentina; ‡ Small Bowel Section and Pathology Service, Municipal Hospital of Gastroenterology, Buenos Aires, Argentina; and § Gastrointestinal Research Group, University of Calgary, Calgary, Alberta, Canada Background & Aims: Intestinal permeability is in- reproducible, and easy to perform. These features, cou- creased in patients with active celiac disease. The pled with the observation that permeability abnormali- measurement of sucrose permeability is proposed as a ties return to normal with treatment, 10,11 make them novel means to detect upper gastrointestinal damage, useful for screening and assessing dietary compliance. with potentially greater use than conventional meth- Sucrose is a disaccharide with a molecular size and ods. The aim of this study was to evaluate the effective- permeation pathway similar to lactulose, but it is rapidly ness of sucrose in the detection of celiac disease. destroyed in the intestine by sucrase-isomaltase. These Methods: Permeability tests were performed in 27 properties suggest that, as a permeability probe, sucrose newly diagnosed patients, at diagnosis, after upper should be very sensitive to proximal gastrointestinal gastrointestinal endoscopies were performed to ex- damage. A recent study showed that this is correct. 12,13 clude macroscopic gastric lesions, and after 2 months Increased sucrose permeability is associated with endo- on a gluten-free diet. Results were compared with scopic gastric damage. However, from a theoretical per- those obtained in 30 healthy subjects and 7 patients with chronic diarrhea but no evidence of celiac disease. spective, patients with celiac disease should also have Results: At diagnosis, 25 of 27 patients had increased increased sucrose permeability. Because they have in- urinary excretion of sucrose. Mean sucrose excretion in creased small intestinal permeability and also decreased patients with untreated celiac disease was significantly dissaccharidase activity, 14 these patients with celiac dis- increased compared with healthy controls and controls ease would be expected to have an increased concentration with disease. Sucrose excretion decreased signifi- of sucrose in the small intestine. In the setting of in- cantly after treatment and completely normalized in creased small intestinal permeability, this should result 60% of patients. The lactulose-mannitol ratio was ab- in increased sucrose recovery in the urine. normal in 26 of 27 patients, with a mean value signifi- While measuring sucrose permeability to detect gas- cantly greater than that observed in healthy controls. tric damage, investigators in the present study observed This ratio also significantly declined after treatment; that several patients with celiac disease were identified however, no values returned to the normal range. Con- clusions: Increased sucrose permeability is a sensitive with increased sucrose permeability, often to extraordi- marker for advanced celiac disease. Moreover, it de- nary degrees. This suggested that this technique may be creases rapidly in response to a gluten-free diet and of value in screening for celiac disease and documenting therefore is potentially useful to follow response to response to therapy. As a probe for the detection of celiac therapy. disease, sucrose has a theoretical advantage over more traditional probes such as lactulose. Nondigestible probes such as lactulose evaluate permeability throughout the A entire small intestine. However, because sucrose is pro- ctive celiac disease is associated with alterations in intestinal permeability. Many studies have de- gressively degraded as it passes through the small intes- scribed increased permeation to cellobiose, 1–3 lactu- tine, it preferentially reports proximal damage because lose, 2,4,5 51 Cr – ethylenediaminetetraacetic acid, 6,7 and oli- that is the only region of the intestine where it remains gosaccharides. 8 In contrast, permeation rates of small intact. Celiac disease is recognized to be primarily a dis- monosaccharides such as mannitol, 2–5,7,8 rhamnose, 9 and ease of the proximal small intestine; therefore, sucrose raffinose are reduced. This has been interpreted as a re- may be very useful in this setting. duction in mucosal surface area and increased permeation of large markers, which is a reflection of epithelial dam- Abbreviation used in this paper: IEL, intraepithelial lymphocyte. age.  1997 by the American Gastroenterological Association 0016-5085/97/$3.00 In general, permeability tests are safe, well tolerated, / 5e1b$$0039 03-14-97 16:15:41 gasa WBS-Gastro