De Smet Els, Mensink Ronald P, Boekschoten Mark V, de Ridder Rogier, Germeraad Wilfred T V, Wolfs Tim G A M, Plat Jogchum
Department of Human Biology,School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University Medical Center,PO Box 616,NL-6200MDMaastricht,The Netherlands.
Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University,Wageningen,The Netherlands.
Br J Nutr. 2015 Mar 14;113(5):794-802. doi: 10.1017/S000711451400350X. Epub 2015 Feb 16.
Plant sterols and stanols inhibit intestinal cholesterol absorption and consequently lower serum LDL-cholesterol (LDL-C) concentrations. The underlying mechanisms are not yet known. In vitro and animal studies have suggested that changes in intestinal sterol metabolism are attributed to the LDL-C-lowering effects of plant stanol esters. However, similar studies in human subjects are lacking. Therefore, we examined the effects of an acute intake of plant stanol esters on gene expression profiles of the upper small intestine in healthy volunteers. In a double-blind cross-over design, fourteen healthy subjects (eight female and six male; age 21-55 years), with a BMI ranging from 21 to 29 kg/m², received in random order a shake with or without plant stanol esters (4 g). At 5 h after consumption of the shake, biopsies were taken from the duodenum (around the papilla of Vater) and from the jejunum (20 cm distal from the papilla of Vater). Microarray analysis showed that the expression profiles of genes involved in sterol metabolism were not altered. Surprisingly, the pathways involved in T-cell functions were down-regulated in the jejunum. Furthermore, immunohistochemical analysis showed that the number of CD3 (cluster of differentiation number 3), CD4 (cluster of differentiation number 4) and Foxp3⁺ (forkhead box P3-positive) cells was reduced in the plant stanol ester condition compared with the control condition, which is in line with the microarray data. The physiological and functional consequences of the plant stanol ester-induced reduction of intestinal T-cell-based immune activity in healthy subjects deserve further investigation.
植物甾醇和甾烷醇可抑制肠道胆固醇吸收,从而降低血清低密度脂蛋白胆固醇(LDL-C)浓度。其潜在机制尚不清楚。体外和动物研究表明,肠道甾醇代谢的变化归因于植物甾烷醇酯的降LDL-C作用。然而,缺乏在人类受试者中的类似研究。因此,我们研究了急性摄入植物甾烷醇酯对健康志愿者上段小肠基因表达谱的影响。在双盲交叉设计中,14名健康受试者(8名女性和6名男性;年龄21 - 55岁),BMI范围为21至29 kg/m²,随机顺序接受含或不含植物甾烷醇酯(4 g)的奶昔。饮用奶昔后5小时,从十二指肠( Vater乳头周围)和空肠(Vater乳头远端20 cm处)取活检组织。微阵列分析表明,参与甾醇代谢的基因表达谱未改变。令人惊讶的是,空肠中参与T细胞功能的通路被下调。此外,免疫组织化学分析表明,与对照条件相比,在植物甾烷醇酯条件下,CD3(分化簇3)、CD4(分化簇4)和Foxp3⁺(叉头框P3阳性)细胞的数量减少,这与微阵列数据一致。植物甾烷醇酯诱导健康受试者肠道基于T细胞的免疫活性降低的生理和功能后果值得进一步研究。