Catry Emilie, Pachikian Barbara D, Salazar Nuria, Neyrinck Audrey M, Cani Patrice D, Delzenne Nathalie M
Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
Life Sci. 2015 Jul 1;132:77-84. doi: 10.1016/j.lfs.2015.04.004. Epub 2015 Apr 25.
Hypolipidemic drugs are prescribed in the most of cases for the treatment of cardiovascular diseases. Several studies have showed that the gut microbiota is able to regulate the host cholesterol metabolism. This study aimed to investigate the potential impact of hypolipidemic drugs on the gut microbiota in mice, and to correlate it to the regulation of cholesterol metabolism.
Male C57Bl/6J mice were divided into four groups fed either a control diet alone (CT), or supplemented with simvastatin (0.1% w/w, Zocor®, MSD), or ezetimibe (0.021% w/w, Ezetrol®, MSD) or a combination of simvastatin and ezetimibe (0.1% and 0.021%, respectively) for one week.
The combination of ezetimibe and simvastatin is required to observe a drop in cholesterolemia, linked to a huge activation of hepatic SREBP-2 and the consequent increased expression of genes involved in LDL cholesterol uptake and cholesterol synthesis. The gut microbiota analysis revealed no change in total bacteria, and in major Gram positive and Gram negative bacteria, but a selective significant increase in Lactobacillus spp. in mice treated with the ezetimibe and a decrease by the combination. The changes in lactobacilli level observed in ezetimibe or combination treated-mice are negatively correlated to expression of genes related to cholesterol metabolism.
The present study showed that ezetimibe taken alone is able to modify the composition of gut microbiota in favor of Lactobacillus spp. These results suggest that members of the genus Lactobacillus play an important role in cholesterol metabolism, even in normocholesterolemic mouse model.
在大多数情况下，降血脂药物被用于治疗心血管疾病。多项研究表明，肠道微生物群能够调节宿主的胆固醇代谢。本研究旨在探讨降血脂药物对小鼠肠道微生物群的潜在影响，并将其与胆固醇代谢的调节相关联。
将雄性C57Bl/6J小鼠分为四组，分别单独喂食对照饮食（CT），或补充辛伐他汀（0.1% w/w，舒降之®，默克雪兰诺公司）、依折麦布（0.021% w/w，益适纯®，默克雪兰诺公司），或辛伐他汀与依折麦布的组合（分别为0.1%和0.021%），持续一周。
需要联合使用依折麦布和辛伐他汀才能观察到胆固醇血症的下降，这与肝脏中SREBP-2的大量激活以及随后参与低密度脂蛋白胆固醇摄取和胆固醇合成的基因表达增加有关。肠道微生物群分析显示，总细菌、主要革兰氏阳性菌和革兰氏阴性菌没有变化，但在用依折麦布治疗的小鼠中乳酸杆菌属有选择性的显著增加，而联合用药则使其减少。在依折麦布或联合用药治疗的小鼠中观察到的乳酸杆菌水平变化与胆固醇代谢相关基因的表达呈负相关。
本研究表明，单独使用依折麦布能够改变肠道微生物群的组成，有利于乳酸杆菌属。这些结果表明，即使在正常胆固醇血症小鼠模型中，乳酸杆菌属成员在胆固醇代谢中也起着重要作用。
