THE CHOLESTEROL-LOWERING EFFECT OF STEROID SEQUESTRANTS IS MODULATED BY LARGE-INTESTINE FERMENTATIONS

The cholesterol lowering effect of steroid sequestring compounds, such as cholestyramine or beta-cyclodextrin, has been examined to assess the respective importance of bile acids excretion and the fermentation process. In contrast to cholestyramine, beta-cyclodextrin is metabolized by the large intestine microflora yielding short chain fatty acids (SCFA), especially propionic acid which is absorbed in the portal vein and metabolized by the liver. beta-cyclodextrin was less potent than cholestyramine at elevating the fecal excretion of bile acids and depressing soluble bile acids in the large intestine but only the former compound was definitely hypocholesterolemic. Changes in circulating lipoproteins (depressed HDL1 and apoE abundance) were observed only in the beta-cyclodextrin-fed group. Cholestyramine was more potent than beta-cyclodextrin to induce the activity of hepatic HMG CoA reductase or cholesterol 7 alpha-hydroxylase, whereas that of fatty acid synthase (FAS) was depressed only in the beta-cyclodextrin group. II appears that fermentable bile acid sequestrants are the most effective at depressing plasma cholesterol, probably in relation to the capacity of fermentation end-products to counteract the upregulation of bile acids and cholesterol biosynthesis.