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首页> 外文学位 >Microencapsulated bile salt hydrolyzing probiotic lactic acid bacteria for use in hypercholesterolemia and associated cardiovascular diseases.
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Microencapsulated bile salt hydrolyzing probiotic lactic acid bacteria for use in hypercholesterolemia and associated cardiovascular diseases.

机译：微囊化胆汁盐水解益生菌乳酸菌，用于高胆固醇血症和相关的心血管疾病。

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摘要

Elevated serum cholesterol, particularly in the low-density lipoprotein (LDL) fraction, is a major independent risk factor for atherosclerosis and coronary artery disease. Current evidence from a variety of human and animal trials suggests a cholesterol lowering effect of specific strains of probiotic lactic acid bacteria; however the results are frequently inconclusive and supportive mechanistic data is scarce. A need therefore exists for low-cost and effective new technologies to meet the present demands and future challenges of probiotics for use in hypercholesterolemia.;The Bio F1B golden Syrian hamster was selected, after species and diet based studies, as a model of hyperlipidemia and cholesterol and bile acid metabolism. Using this model, orally delivered microencapsulated genetically engineered L. plantarum 80 strain significantly lowered total and LDL cholesterol, and improved the atherogenic profile associated with hypercholesterolemia. The effectiveness of the formulation was shown to be dependent on dose and frequency of administration. Furthermore, heart histological samples confirmed a protective effect. Microencapsulated bile salt hydrolase active L. reuteri, chosen among naturally occurring candidate strains, was shown to also lower serum lipids at equivalent dosage, albeit with a significant lag effect towards LDL cholesterol. Treated groups showed increased fecal bile salt excretion along with a significant shift in biliary lipid components compared to control animals, likely due to an up-regulation of hepatic bile acid synthesis from cholesterol.;This work demonstrates the potential effectiveness of this approach as a means of preventing or treating hypercholesterolemia in humans. Furthermore, safety studies indicate that side effects often associated with currently used pharmacologics are largely avoided.;In this thesis, microcapsule formulations for the entrapment of genetically engineered and non-genetically engineered lactic acid bacteria with elevated bile salt hydrolase activity were designed and developed. Strain specific microencapsulation techniques were used to produce spherical microcapsules with narrow size distribution and high cell loading. By enhancing the micro-environment of the encased strains, a high number of viable cells were delivered to the intestine with protection from acid, bile and mechanical stresses. Furthermore, enzymatic activity towards conjugated bile salt substrates was maintained, with significant preference for glyco-conjugates, when administered through a dynamic model simulating human gastrointestinal (GI) transit.
机译：血清胆固醇升高，尤其是低密度脂蛋白（LDL）分数升高，是动脉粥样硬化和冠状动脉疾病的主要独立危险因素。来自各种人类和动物试验的最新证据表明，特定菌株的益生菌乳酸菌具有降低胆固醇的作用。然而，结果常常是不确定的，并且缺乏支持性的机械数据。因此，需要一种低成本，有效的新技术来满足用于高胆固醇血症的益生菌的当前需求和未来挑战。;经过种类和饮食研究后，选择了Bio F1B金色叙利亚仓鼠作为高脂血症的模型和胆固醇和胆汁酸代谢。使用该模型，口服递送的微囊化基因工程植物乳杆菌80菌株显着降低了总胆固醇和LDL胆固醇，并改善了与高胆固醇血症相关的动脉粥样硬化。已显示出制剂的有效性取决于给药的剂量和频率。此外，心脏组织学样本证实具有保护作用。从天然候选菌株中选出的微囊化胆汁盐水解酶活性罗伊氏乳杆菌，即使对LDL胆固醇有显着的滞后作用，也能以相同的剂量降低血清脂质。与对照组相比，治疗组的粪便胆汁盐排泄增加，胆汁脂质成分发生明显变化，这可能是由于胆固醇引起的肝胆汁酸合成上调所致。这项工作证明了这种方法作为一种手段的潜在有效性。预防或治疗人的高胆固醇血症。此外，安全性研究表明，可以很大程度上避免经常与当前使用的药理学相关的副作用。在本论文中，设计并开发了微胶囊制剂，用于捕获具有升高的胆汁盐水解酶活性的基因工程和非基因工程乳酸菌。应变特异性微囊化技术被用于生产具有窄尺寸分布和高细胞负荷的球形微囊。通过增强被包裹菌株的微环境，在抵抗酸，胆汁和机械应力的保护下，大量活细胞被递送到肠中。此外，当通过模拟人胃肠（GI）转运的动态模型施用时，维持对缀合的胆汁盐底物的酶活性，其中糖缀合物具有显着的偏好。

著录项

  • 作者

    Martoni, Christopher John.;

  • 作者单位

    McGill University (Canada).;

  • 授予单位 McGill University (Canada).;
  • 学科 Engineering Biomedical.;Biology Physiology.;Biology Microbiology.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 278 p.
  • 总页数 278
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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