CALCIUM REDUCES THE INCREASED FECAL 1,2-SN-DIACYLGLYCEROL CONTENT IN INTESTINAL-BYPASS PATIENTS - A POSSIBLE MECHANISM FOR ALTERING COLONICHYPERPROLIFERATION

Diacylglycerol (DAG) is a second messenger for protein kinase C, an en zyme with a key role in cellular signal transduction and growth contro l. In previous studies, it was demonstrated that DAG is produced by in testinal microflora. Bacterial DAG production is increased by bile aci ds and phospholipids, both of which may be precipitated by calcium. We have demonstrated that fecal total lipids, bile acids, and rectal epi thelial proliferation are increased in intestinal bypass (IB) patients . Calcium was shown to alter fecal lipid composition and to reduce cel l proliferation. In the present study, fecal DAG content and C-14-labe led DAG,C-14-phosphatidylcholine, and C-14-phosphatidylinositol metabo lism were measured in 24-h stool collections in 15 stable IB patients before and after 3-month therapy with Oral elemental calcium, 2.4 or 3 .6 g/day. Fecal DAG concentration and output in IB patients were >25- and >200-fold greater than in normal controls. Oral calcium markedly r educed fecal DAG concentration and output and increased DAG, phosphati dylcholine, and phosphatidylinositol metabolism without enhancing DAG production. We conclude that fecal DAG content is markedly elevated po st-IB and that calcium supplementation in these patients reduces fecal DAG and accelerates bacterial metabolism of DAG and its precursors. I n separate studies, we have found that calcium supplementation also de creases rectal hyperproliferation in IB patients. Taken together these findings suggest that a high luminal level of DAG enhances colonic ce ll proliferation and that calcium reduces cell proliferation in part b y decreasing the level of DAG.