Lectins can reverse the distal intestinal atrophy associated with elemental diets in mice M. SASAKI*, A. J. FITZGERALD*, G. GRANT  , M. A. GHATEI à , N. A. WRIGHT* & R. A. GOODLAD§ *Department of Histopathology, Imperial College School of Medicine, Hammersmith Hospital, London, UK;  Rowett Research Institute, Bucksburn, Aberdeen, UK; àDepartment of Metabolic Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, UK; and §Histopathology Unit, Imperial Cancer Research Fund, London, UK Accepted for publication 7 September 2001 INTRODUCTION Treatment with elemental diets can provide signi®cant clinical bene®ts, and they are widely used as therapy for in¯ammatory bowel disease and in post-operative patients. Elemental diet therapy is recognized as a primary therapy in Crohn's disease; however, intestinal atrophy is one of the complications associated with the use of elemental diets, as is also observed following total parenteral nutrition. 1 This atrophy can weaken the integrity of the gut and may lead to increased intestinal permeability and bacterial translocation. 2, 3 The control of cell renewal in the gastrointestinal tract is complex and multifactorial, but the most important factor is luminal nutrition or intestinal workload, in which the presence of nutrients within the bowel stimulates mucosal growth. This may occur directly, which has been suggested for some nutrients, such as glutamine and the short-chain fatty acids, or the mechanism may be indirect. Such indirect mechanisms could involve systemic factors, such as hormones, or more local agents, such as the several growth factors which are present both within the gastrointestinal secretions and in the mucosa. SUMMARY Background: Elemental diets cause intestinal atrophy and reduced intestinal integrity, which can lead to signi®cant increases in intestinal permeability and bacterial translocation. Recently, several lectins have been shown to have trophic effects on the intestine. Aims: We examined the effects of concanavalin-A and phytohaemagglutinin on cell proliferation and crypt ®ssion throughout the intestine of mice fed on elemental diets. Methods: Mice were randomized to chow fed, elemental diet, elemental diet plus concanavalin-A and elemental diet plus phytohaemagglutinin groups. Cell proliferation and crypt ®ssion were estimated in microdissected crypts. Plasma gastrin and enteroglucagon levels were measured by radioimmunoassay. Results: Elemental diet feeding signi®cantly decreased cell proliferation and crypt ®ssion of the middle and distal small intestine and throughout the colon. Phyto- haemagglutinin signi®cantly increased the weight of the intestine, but concanavalin-A had little effect. Cell proliferation in the small intestine was signi®cantly increased by both lectins. However, in the stomach and colon, only phytohaemagglutinin increased prolifer- ation. Crypt ®ssion in the colon was dramatically increased by phytohaemagglutinin. Phytohaemaggluti- nin increased the plasma gastrin level, but not the enteroglucagon level. Conclusions: Lectins have signi®cant trophic effects on the small intestine and colon of mice fed elemental diets, and these actions vary between different sites in the gastrointestinal tract. Correspondence to: Dr R. A. Goodlad, Imperial Cancer Research Fund, Histopathology Unit, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK. E-mail: goodlad@icrf.icnet.uk Aliment Pharmacol Ther 2002; 16: 633±642. Ó 2002 Blackwell Science Ltd 633