Disaccharidase Activity and Jejunal Morphology in Coeliac Disease

Abstract

The disaccharidases of the small-intestinal mucosa are located in the microvilli of the epithelial absorptive cells and are readily estimated in homogenates of jejunal biopsy specimens. When the jejunal mucosa is diffusely damaged, as in untreated coeliac disease, all the disaccharidase activity is markedly depressed. The corollary is that the disaccharidases provide an index of the degree of recovery when a disease such as coeliac disease is given appropriate treatment. In the present study 45 patients with untreated coeliac disease were studied by jejunal biopsy, which plays a crucial role in the diagnosis of the disease. All these patients had a jejunal mucosa which appeared ‘flat’ under the dissecting microscope and all showed the corresponding changes of severe villous atrophy and crypt hyperplasia on light microscopy. All the disaccharidases were greatly depressed when compared with the findings in a group of healthy volunteers. In 10 of these patients, jejunal biopsy was repeated at least once after they had been placed on a gluten-free diet and were, to the best of our knowledge, adhering strictly to it. All showed evidence of morphological recovery, which was assessed by a quantitative histological method. As far as the disaccharidases are concerned, the maltase and sucrase usually showed rapid recovery and reached normal levels of activity within a few months. The response of lactase was much more variable, sometimes showing full recovery in a few months but sometimes remaining severely depressed for years. The age of the patient was of great importance in the rate of recovery of lactase activity, with patients aged less than 30 years usually showing full recovery in the course of a few months whereas most of the older patients showed little or no recovery in this space of time. In one patient, an elderly woman who had shown an excellent clinical response to a gluten-free diet but in whom the jejunal mucosa remained morphologically abnormal and with severely depressed disaccharidase activity, the effect of a two-month course of cortico-steroids was studied. There was morphological improvement and enhanced disaccharidase activity, but reversion on cessation of the cortico-steroid treatment. Prolonged follow-up with repeated jejunal biopsy showed a very slow morphological and enzymatic recovery. In two of the patients who had made a perfect clinical, morphological, and enzymatic recovery on a gluten-free diet, the effect of reintroducing ordinary bread into the diet has been studied by serial biopsy. Both showed a rapid morphological deterioration of the jejunal mucosa which was accompanied by severe depression of disaccharidase activity. Neither experienced any symptoms while this histological and biochemical disturbance was occurring. Subsequent return to a gluten-free diet was followed by evidence of recovery. These observations demonstrate that, although a patient with coeliac disease may be able to tolerate gluten from a symptomatic viewpoint, the gluten always damages the jejunal mucosa. The corollary is that patients with coeliac disease should remain permanently on a gluten-free diet.