Prebiotics, Gut Microbiota, and Cardiometabolic Health

益生元、肠道微生物群和心脏代谢健康

• 批准号: 9037148
• 负责人: KEVIN P DAVY
• 金额: $ 8.18万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9037148
• 关键词: Adoption; Adult; Age-Years; Basic Science; Behavior; Behavior Therapy; Bifidobacterium; Biological Assay; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Chronic; Communities; Data; Detection; Development; Diabetes Mellitus; Diet; Dietary Fiber; Dietary intake; Dilatation - action; Endotoxins; Event; Exercise; Fatty Acids; Food; Functional disorder; Future; Generations; Glucose; Growth; Health; Human; Individual; Inflammation; Intake; Intervention Studies; Intestines; Inulin; Investigation; Lead; Lipopolysaccharides; Maintenance; Measurement; Measures; Mediating; Medical; Metabolic; Non-Insulin-Dependent Diabetes Mellitus; Permeability; Physiological; Placebos; Prediabetes syndrome; Pyruvate; Randomized; Recombinant DNA; Recommendation; Resolution; Risk; Rodent; Rodent Model; Serum; Skeletal Muscle; Supplementation; Ultrasonography; Woman; Work; arterial stiffness; cardiometabolic risk; cardiovascular disorder risk; clinical practice; double-blind placebo controlled trial; experience; factor C; flexibility; gastrointestinal epithelium; gut microbiota; improved; innovation; insulin sensitivity; intravenous glucose tolerance test; lifestyle intervention; maltodextrin; men; microbial; nutrition; oxidation; prebiotics; prevent; pyrosequencing; success; sugar; tonometry; Adoption; Adult; Age-Years; Basic Science; Behavior; Behavior Therapy; Bifidobacterium; Biological Assay; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Chronic; Communities; Data; Detection; Development; Diabetes Mellitus; Diet; Dietary Fiber; Dietary intake; Dilatation - action; Endotoxins; Event; Exercise; Fatty Acids; Food; Functional disorder; Future; Generations; Glucose; Growth; Health; Human; Individual; Inflammation; Intake; Intervention Studies; Intestines; Inulin; Investigation; Lead; Lipopolysaccharides; Maintenance; Measurement; Measures; Mediating; Medical; Metabolic; Non-Insulin-Dependent Diabetes Mellitus; Permeability; Physiological; Placebos; Prediabetes syndrome; Pyruvate; Randomized; Recombinant DNA; Recommendation; Resolution; Risk; Rodent; Rodent Model; Serum; Skeletal Muscle; Supplementation; Ultrasonography; Woman; Work; arterial stiffness; cardiometabolic risk; cardiovascular disorder risk; clinical practice; double-blind placebo controlled trial; experience; factor C; flexibility; gastrointestinal epithelium; gut microbiota; improved; innovation; insulin sensitivity; intravenous glucose tolerance test; lifestyle intervention; maltodextrin; men; microbial; nutrition; oxidation; prebiotics; prevent; pyrosequencing; success; sugar; tonometry

DESCRIPTION (provided by applicant): Prediabetes is associated with a low grade chronic inflammation which increases the risk, not only for developing type 2 diabetes (T2DM), but also for suffering from cardiovascular disease (CVD)-related events. An elevated lipopolysaccharide (or endotoxin) concentrations, associated with dysbiosis of the intestinal microbiota, has been implicated in the development of both T2DM and CVD. Selective modulation of the intestinal microbiota with prebiotics reduces intestinal permeability and endotoxin concentrations, systemic and local inflammation, and metabolic dysfunction in rodent models. The effect of prebiotic supplementation on cardiometabolic function in prediabetic humans is not known. The general objectives of this R21 proposal are to: 1) determine the feasibility and establish proof-of-concept for the effects of supplementation with the prebiotic inulin on cardiometabolic function in prediabetic humans in order to conduct a larger, more comprehensive randomized double-blind placebo- controlled trial in the future; 2) establish our proficiency with measurements of intestinal permeability and characterizing fecal bacterial composition; and 3) obtain preliminary data for effect size generation. To this end, we will randomize 48 prediabetic adults (50-75 yrs) to 4 weeks of prebiotic supplementation with inulin (10 g/day) or placebo (maltodextrin). Subjects will be provided with all of their food for the duration of the study from our metabolic kitchen to avoid potential confounding through differences in dietary intake between individuals. Measurements of intestinal permeability (sugar probes), serum endotoxin concentrations (Factor C Endotoxin Detection Assay), insulin sensitivity (intravenous glucose tolerance testing), skeletal muscle metabolic flexibility (ex vivo fatty acid, glucose and pyruvate oxidation), endothelial function (flow-mediated dilatation), arterial stiffness (applanation tonometry and high resolution ultrasound), and fecal bacterial composition (16S rDNA pyrosequencing) will be measured at baseline and following 4 weeks of treatment. This innovative integrative and translational physiological study will be conducted by an established P.I. and investigative team with extensive experience and a strong record of success performing intervention studies targeting cardiometabolic dysfunction. These studies have significant translational potential as they may advance basic science findings in rodents to humans. The identification of prebiotic supplementation with inulin as a simple and efficacious adjunctive strategy for reducing cardiometabolic risk in prediabetics could change clinical practice by informing dietary recommendations and increasing acceptance of prebiotics by the scientific and medical community.

描述（由申请人提供）： 糖尿病前期与低级慢性炎症有关，这不仅增加了2型糖尿病（T2DM），而且还与患有心血管疾病（CVD）相关的事件的疾病有关。与肠道菌群营养不良有关的脂多糖（或内毒素）浓度升高，与T2DM和CVD的发展有关。选择性调节肠道菌群具有前益生元可降低肠道渗透性和内毒素浓度，全身性和局部炎症以及啮齿动物模型中代谢功能障碍。尚不清楚益生元补充对糖尿病前代谢功能的影响。该R21提案的一般目标是：1）确定可行性并确定概念概念的概念概念，以补充益生蛋白依他蛋白对糖尿病前期的心脏代谢功能的补充作用，以便在未来进行更大，更全面的随机性双盲安慰剂 - 未来。 2）通过测量肠道通透性和表征粪便细菌组成的测量； 3）获取效果尺寸产生的初步数据。为此，我们将用含糖蛋白（10 g/day）或安慰剂（麦芽糊精）随机将48名糖尿病前成年人（50 - 75年）（50 - 75年）到4周。 在我们的代谢厨房的研究期间，将为受试者提供所有食物，以避免因个人之间饮食摄入的差异而产生的混淆。测量肠道通透性（糖探针），血清内毒素浓度（因子C内毒素检测测定），胰岛素敏感性（静脉葡萄糖耐受性测试），骨骼肌代谢柔韧性（骨骼肌代谢柔韧性）（过度脂肪酸酸，葡萄糖和丙酮酸氧化），抗速溶性氧化（原始氧化）（流动性）（流动性）（流动性）（流动性）（流动性（流动性）（流动性）（流动性）功能（流动性（流动性）功能（流动性）功能（流动性）（流动性）功能（流动性）功能（流动性）功能（流动性（流动性）功能（流动性）功能（杂种）功能（流动性（流动性）功能（流动性）功能（流动性）功能（杂种型）功能（杂种功能（流动性） Tonometry和高分辨率超声）和粪便细菌组成（16S rDNA pyrosequencing）将在基线和治疗4周后测量。这项创新的综合和转化生理研究将由已建立的P.I进行。以及具有丰富经验的调查团队，并有良好的记录，以实现心脏代谢功能障碍进行干预研究的成功记录。这些研究具有巨大的转化潜力，因为它们可能会推动啮齿动物对人类的基础科学发现。用菊粉补充益生元的鉴定为一种简单有效的辅助策略，用于降低糖尿病前期心脏代谢风险，可以通过告知饮食建议并通过科学和医学界增加对益生元的接受来改变临床实践。