Prebiotics, Gut Microbiota, and Cardiometabolic Health
益生元、肠道微生物群和心脏代谢健康
基本信息
- 批准号:8812501
- 负责人:
- 金额:$ 7.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-01-01 至 2015-12-31
- 项目状态:已结题
- 来源:
- 关键词:AdoptionAdultAge-YearsBasic ScienceBehaviorBehavior TherapyBifidobacteriumBiological AssayCardiovascular DiseasesCardiovascular PhysiologyCardiovascular systemChronicCommunitiesDataDetectionDevelopmentDiabetes MellitusDietDietary FiberDietary intakeDilatation - actionEndotoxinsEventExerciseFatty AcidsFoodFunctional disorderFutureGenerationsGlucoseGrowthHealthHumanIndividualInflammationIntakeIntervention StudiesIntestinesInulinInvestigationLeadLipopolysaccharidesMaintenanceMeasurementMeasuresMediatingMedicalMetabolicNon-Insulin-Dependent Diabetes MellitusPermeabilityPhysiologicalPlacebosPrediabetes syndromePyruvateRandomizedRecombinant DNARecommendationResolutionRiskRodentRodent ModelSerumSkeletal MuscleSupplementationUltrasonographyWomanWorkarterial stiffnesscardiovascular disorder riskclinical practicedouble-blind placebo controlled trialexperiencefactor Cflexibilitygastrointestinal epitheliumgut microbiotaimprovedinnovationinsulin sensitivityintravenous glucose tolerance testlifestyle interventionmaltodextrinmenmicrobialnutritionoxidationprebioticspreventpyrosequencingsuccesssugartonometry
项目摘要
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):
糖尿病前期与低度慢性炎症有关,这不仅会增加患 2 型糖尿病 (T2DM) 的风险,还会增加患心血管疾病 (CVD) 相关事件的风险。脂多糖(或内毒素)浓度升高与肠道微生物群失调相关,与 T2DM 和 CVD 的发生有关。在啮齿动物模型中,益生元选择性调节肠道微生物群可降低肠道通透性和内毒素浓度、全身和局部炎症以及代谢功能障碍。补充益生元对糖尿病前期人群心脏代谢功能的影响尚不清楚。该 R21 提案的总体目标是:1) 确定补充益生元菊粉对糖尿病前期人群心脏代谢功能的影响的可行性并建立概念验证,以便进行更大规模、更全面的随机双盲研究未来进行安慰剂对照试验; 2) 建立我们对肠道通透性测量和粪便细菌组成特征的熟练程度; 3) 获得效应量生成的初步数据。为此,我们将 48 名糖尿病前期成人(50-75 岁)随机分组,接受 4 周的益生元补充,菊粉(10 克/天)或安慰剂(麦芽糖糊精)。 在研究期间,我们的代谢厨房将为受试者提供所有食物,以避免个体之间饮食摄入差异造成的潜在混淆。肠道通透性测量(糖探针)、血清内毒素浓度(C因子内毒素检测分析)、胰岛素敏感性(静脉葡萄糖耐量测试)、骨骼肌代谢灵活性(离体脂肪酸、葡萄糖和丙酮酸氧化)、内皮功能(血流-介导的扩张)、动脉硬度(压平眼压测量和高分辨率超声)和粪便细菌成分(16S rDNA 焦磷酸测序)将在基线和随后进行测量治疗4周。这项创新的综合和转化生理学研究将由一位知名的 P.I. 进行。以及具有丰富经验和针对心脏代谢功能障碍进行干预研究的良好记录的研究团队。这些研究具有重大的转化潜力,因为它们可能会将啮齿类动物的基础科学发现推广到人类。确定用菊粉补充益生元作为降低糖尿病前期患者心脏代谢风险的简单而有效的辅助策略,可以通过提供膳食建议和提高科学界和医学界对益生元的接受度来改变临床实践。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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KEVIN P DAVY其他文献
KEVIN P DAVY的其他文献
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{{ truncateString('KEVIN P DAVY', 18)}}的其他基金
Vascular Consequences of Ultra-Processed Foods in Middle-Aged Adults
超加工食品对中年人血管的影响
- 批准号:
10683369 - 财政年份:2022
- 资助金额:
$ 7.92万 - 项目类别:
Vascular Consequences of Ultra-Processed Foods in Middle-Aged Adults
超加工食品对中年人血管的影响
- 批准号:
10532576 - 财政年份:2022
- 资助金额:
$ 7.92万 - 项目类别:
Gut Microbiota, Trimethylamine N-Oxide, and Endothelial Dysfunction in Middle-Aged Adults
中年成人肠道微生物群、氧化三甲胺和内皮功能障碍
- 批准号:
9789801 - 财政年份:2018
- 资助金额:
$ 7.92万 - 项目类别:
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:
8644352 - 财政年份:2014
- 资助金额:
$ 7.92万 - 项目类别:
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 - 财政年份:2014
- 资助金额:
$ 7.92万 - 项目类别:
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:
8786598 - 财政年份:2014
- 资助金额:
$ 7.92万 - 项目类别:
Angiotensin II Receptor Blockade and Adipose Tissue Inflammation in Obesity
肥胖症中血管紧张素 II 受体阻断和脂肪组织炎症
- 批准号:
7531877 - 财政年份:2008
- 资助金额:
$ 7.92万 - 项目类别:
Angiotensin II Receptor Blockade and Adipose Tissue Inflammation in Obesity
肥胖症中血管紧张素 II 受体阻断和脂肪组织炎症
- 批准号:
7672464 - 财政年份:2008
- 资助金额:
$ 7.92万 - 项目类别:
Visceral Fat and Autonomic-Circulatory Control in Humans
人类内脏脂肪和自主循环控制
- 批准号:
6790287 - 财政年份:2003
- 资助金额:
$ 7.92万 - 项目类别:
Visceral Fat and Autonomic-Circulatory Control in Humans
人类内脏脂肪和自主循环控制
- 批准号:
6726830 - 财政年份:2003
- 资助金额:
$ 7.92万 - 项目类别:
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