Plant Stanols and Gene Expression Profile

The Effects of Plant Stanol Esters on Intestinal Mucosal Gene Expression Profiles and Microbiota Composition in Healthy Human Subjects

Plant sterols and stanols are dietary components that are naturally present in plants. Their biological function in plants is comparable with these of cholesterol in animals. They are structurally related to cholesterol, but are absorbed by enterocytes to a much lesser extent. It is generally accepted that they inhibit intestinal cholesterol absorption and consequently lower serum low-density lipoprotein (LDL) cholesterol concentrations up to 10% at daily intakes of 2.5 g. The exact underlying mechanism of the plant sterol/stanol mediated reduction in intestinal cholesterol absorption is still unknown. It has been suggested that they lower the activity of sterol uptake transporters like Niemann-Pick C1 like 1 protein (NPC1L1) in enterocytes, otherwise several studies indicated that these compounds could activate the liver X receptor (LXR) in enterocytes, thereby activating the ABC transporters involved in the intestinal cholesterol metabolism, whereas recently suggestions have been made that plant sterols and stanols activate transintestinal cholesterol excretion (TICE). This is the direct cholesterol secretion from the blood into the intestinal lumen, in which the enterocytes play a central role. None of these assumptions have so far been evaluated in humans. Objective: The major objective of the present study is to examine the acute effects of dietary plant stanol esters on the intestinal mucosal gene expression profiles in intestinal biopsies in healthy volunteers. The minor objective is to investigate whether semi-long-term use (3 weeks) of plant stanol esters have an effect on microbiota composition.

lant sterols and stanols are dietary components that are naturally present in plants. Their biological function in plants is comparable with these of cholesterol in animals. They are structurally related to cholesterol, but are absorbed by enterocytes to a much lesser extent. It is generally accepted that they inhibit intestinal cholesterol absorption and consequently lower serum low-density lipoprotein (LDL) cholesterol concentrations up to 10% at daily intakes of 2.5 g. The exact underlying mechanism of the plant sterol/stanol mediated reduction in intestinal cholesterol absorption is still unknown. It has been suggested that they lower the activity of sterol uptake transporters like Niemann-Pick C1 like 1 protein (NPC1L1) in enterocytes, otherwise several studies indicated that these compounds could activate the liver X receptor (LXR) in enterocytes, thereby activating the ABC transporters involved in the intestinal cholesterol metabolism, whereas recently suggestions have been made that plant sterols and stanols activate transintestinal cholesterol excretion (TICE). This is the direct cholesterol secretion from the blood into the intestinal lumen, in which the enterocytes play a central role. None of these assumptions have so far been evaluated in humans. Objective: The major objective of the present study is to examine the acute effects of dietary plant stanol esters on the intestinal mucosal gene expression profiles in intestinal biopsies in healthy volunteers. The minor objective is to investigate whether semi-long-term use (3 weeks) of plant stanol esters have an effect on microbiota composition.

Subjects will undergo a postprandial test for 5.5 hours, in which 26.7gram of the control margarine is consumed together with a high-fat milkshake. Daily consumption of 20 gram of a control margarine (providing daily 3.0 gram of plant stanols), for a period of 3 weeks.

Subjects will undergo a postprandial test for 5.5 hours, in which 26.7gram of the plant stanol-enriched margarine is consumed together with a high-fat milkshake. Daily consumption of 20 gram of a plant stanol-enriched margarine (providing daily 3.0 gram of plant stanols), for a period of 3 weeks.

measured after 3 weeks consumption of controle margarine and the plant stanol-enriched margarine. Changes will be calculated between these 2 interventions.

Inclusion Criteria: Aged between 18-60 years BMI between 20-30kg/m2 mean serum total cholesterol < 7.8mmol/L Exclusion Criteria: unstable body weight active cardiovascular diseases gastrointestinal diseases use of cholesterol-lowering drugs use of lipid-lowering therapy abuse of drug or alcohol pregnant or breast-feeding women current smoker