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Cellobiose/Mannitol Sugar Permeability Test Complements Biopsy Histopathology in Clinical Investigation of the Jejunum

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Cellobiose/Mannitol Sugar Permeability Test Complements Biopsy Histopathology in Clinical Investigation of the Jejunum Gut: first published as 10.1136/gut.25.11.1241 on 1 November 1984. Downloaded from Gut, 1984, 25, 1241-1246 Cellobiose/mannitol sugar permeability test complements biopsy histopathology in clinical investigation of the jejunum S STROBEL, W G BRYDON, AND ANNE FERGUSON From the Gastro-Intestinal Unit, University ofEdinburgh and Western General Hospital, Edinburgh, Scotland SUMMARY Intestinal permeability to probe molecules has been shown to correlate closely with the presence or absence of villous atrophy in a jejunal biopsy. The purpose of this study was to establish if there exist groups of patients with functional derangement of intestinal permeability but normal histopathology of the small bowel mucosa. In 135 patients a cellobiose/mannitol permeability test was performed at the same time as jejunal biopsy. Diagnosis included coeliac disease, Crohn's disease, irritable bowel syndrome, idiopathic diarrhoea, self diagnosed food allergy, atopic eczema and postinfectious malabsorption. The value of the cellobiose/mannitol test in identifying patients with abnormal jejunal biopsy histopathology was confirmed. The permeability test was abnormal in all 28 patients with partial or subtotal villous atrophy, and also in all 10 in whom there was a high intraepithelial lymphocyte count despite normal villi and crypts. Functional abnormality of the small intestine has not previously been reported in patients with this jejunal biopsy abnormality. Abnormalities of permeability were also found in patients with idiopathic diarrhoea, folate deficiency, postinfectious or traveller's diarrhoea, small bowel Crohn's disease, and atopic eczema. These results show that sugar permeability tests have more potential in clinical investigation than merely serving as screening tests before jejunal biopsy. There are groups of patients without morphological changes in the small bowel in whom http://gut.bmj.com/ intestinal permeability is abnormal. Several abnormal features of transepithelial trans- In the initial clinical assessments of these in diseases of the small intestine several with non-coeliac port occur permeability tests, patients on September 24, 2021 by guest. Protected copyright. associated with villous atrophy. These include gastrointestinal disease6 7 or with atopic eczema8 impairment in active absorption of various have been described, in whom permeability ratios nutrients, reduction in the passive penetration of the are abnormal. Thus there may exist groups of epithelium by small probe molecules and an increase patients with functional derangement of intestinal in the permeability to larger molecules of molecular permeability, in which the bowel is 'leaky' to large radius greater than 0 5 nm. Such observations form probes, even though histopathology is normal. the theoretical basis for several recently described Clearly, this could provide an entirely new approach tests of intestinal permeability,1-3 which measure to investigation of disorders of the jejunum although the absorption or penetration of large and small it will remain essential to interpret the results of probe molecules. The ratio of permeability for large such permeability tests in the knowledge of versus small probes is increased in patients with intestinal histopathology. We have performed, coeliac disease-5 and it has been suggested that an simultaneously, jejunal biopsy and a cellobiose/ intestinal permeability test will provide one method mannitol sugar permeability test in order to for screening patients who should be submitted to determine if indeed these tests are complementary. jejunal biopsy.6 One hundred and thirty five patients were investigated, all of whom were undergoing Address for correspondence: Dr Stephan Strobel, Gastro-Intestinal Unit, investigation of diarrhoeal disease, malabsorption Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland. or possible food allergy. The results show not only Received for publication 15 February 1984 that the sugar permeability test will predict all 1241 Gut: first published as 10.1136/gut.25.11.1241 on 1 November 1984. Downloaded from 1242 Strobel, Brydon, and Ferguson patients with abnormal jejunal histopathology, but staffed by nurses. After an overnight fast the patient also that there exist a group of distinct clinical and reported at about 8 am, emptied his bladder and pathological entities, where sugar permeability is then swallowed a prepared Watson peroral biopsy abnormal despite unequivocally normal jejunal capsule, with a few sips of water. Fifteen milligrams biopsy histopathology. metochlopromide was given orally. Five minutes later the patient started to drink the sugar test Methods solution, and this was consumed within five minutes. The position of the biopsy capsule was monitored by PATIENTS AND VOLUNTEERS screening and when the capsule was beyond the Fifteen normal volunteers who had not had jejunal ligament of Treitz, a biopsy was taken in the usual biopsy (healthy laboratory and medical staff) age way and the capsule withdrawn. Patients fasted for a range 21-42 years, were used to establish a total of five hours after ingestion of the sugar test provisional normal range for the test. As the test. solution, with the exception of water, tea or coffee solution contained lactose, a further five doctors, all without milk or sugar which were allowed after 21 clinically lactose malabsorbers (assessed by the hours. All urine passed within five hours of the sugar breath hydrogen test after a lactose load) also drink was collected, the volume measured and an participated in the test. aliquot stored at -20°C. The composition of the sugar test solution was as follows: 2 g mannitol, 5 g BIOPSIED PATIENTS cellobiose, 20 g lactose, 20 g sucrose made up to 150 Patients undergoing jejunal biopsy for conventional ml with tap water to §ive an osmolality of clinical indications - diarrhoea, suspected approximately 1500 mosm. malabsorption, follow up of treated coeliac disease The jejunal biopsy was examined with a dissecting and possible food allergic disease - comprised the microscope and processed for conventional histo- study group. There were 135 patients, an unselected pathological diagnosis. Subsequently all slides were sequential series of patients, whose ages ranged coded and reviewed. The histology was classified as from 14-75 years. After the study had been either unequivocally abnormal with partial or completed, case notes were reviewed retrospectively subtotal villous atrophy; essentially normal with and a final diagnosis made on the basis of all the normal villus and crypt architecture but with a high clinical information including the result of the intraepithelial lymphocyte count (>40 lymphocytes/ jejunal biopsy histopathology and disaccharidase 100 epithelial cells);9 and completely normal, with http://gut.bmj.com/ assays but without knowledge of the result of the normal villus crypt architecture and normal intra- sugar permeability test. The final diagnoses are epithelial lymphocyte count. Disaccharidases listed in Table 1. lactase, sucrase, trehalase and maltase were assayed by Dahlqvist's method.'0 INVESTIGATIVE PROCEDURES The procedures were performed mainly in out MANNITOL AND CELLOBIOSE ASSAYS patients, who attend a clinical investigation suite Mannitol Mannitol in urine was measured by the method of on September 24, 2021 by guest. Protected copyright. Corcoran and Page," and is oxidised to Table 1 Diagnoses in volunteers and patients formaldehyde by periodic acid. The formaldehyde reacts with chromotropic acid to form a purple Non-biopsied complex which is measured at 570 nm absorbance. N - Normal volunteers 15 L - Lactase deficient clinical staff 5 Biopsied Cellobiose N - Normal (volunteers and healthy relatives of A new method, suitable for routine clinical coeliacs) 9 diagnostic laboratories was developed - this avoided IBS - Irritable bowel syndrome 15 a need for quantitative paper chromatography. ID - Idiopathic diarrhoea 10 'FA' - Self diagnosed food allergy - not substantiated on Cellobiose reacted with B-glucosidase to yield two clinical investigation 9 molecules of glucose/cellobiose molecule. D-glucose AE - Atopic eczema 13 was then measured using the hexokinase procedure Cr - Small intestinal Crohn's disease 7 with NADPH generation measured at 340 nm (see UC - Ulcerative colitis 3 I - Postinfectious diarrhoea (+ bacterial colonisation) 7 appendix). The hyperosmolar sugar solution used H - Folate deficiency (presumed nutritional) 5 for this procedure was similar to several previously M - Miscellaneous gastrointestinal disorders 17 published studies and contained 20 g lactose. The ND - Coeliac disease (normal diet) 13 Sigma used in the measurement of GFD - Gluten free diet prescribed 27 B-glucosidase cellobiose had lactose hydrolytic activity. In order to Gut: first published as 10.1136/gut.25.11.1241 on 1 November 1984. Downloaded from Jejunal permeability and biopsy histology 1243 Table 2 Urinary recoveries ofcellobiose and mannitol (total and % ingested doselS hours) in normals andpatients Disease MannitollS h x±SD (g) Cellobiosel5 h x±SD (g) Mannitol % x+SD Cellobiose % x±SD Not Normal volunteers 0-47±0-12 0-027±0-008 23-3±5-0 0-54±0-16 15 (0-39±0.17)* (0.016±0.01) (19-6±8-3) (0-32±0.20) Irritable bowel syndrome 0-42±0-012 0-026±0-012 21-0±5-8 0-51±0-25 11 Eczema (with C/M ratio) 0-31±0-12 0-041±0-013 15-6±6-2 0-82±0-26 4 Coeliac disease 0-25±0-11 0-064±0-045 12-5±5-5 1-27±0-9 27 (0-17±0.13) (0-048±0-031) (8.3±6-3) (0-96±0-61) Crohn's disease 0-28±0-11 0-043±0-017 14.2±5-4
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