Health promoting effects of high-polyphenol foods may be mediated through gut microbiome

高多酚食物的健康促进作用可能是通过肠道微生物介导的

基本信息

批准号：
9398518
负责人：
ILYA RASKIN
金额：
$ 0.52万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-02-01 至 2020-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9398518
关键词：
ANGPTL4 gene Anaerobic Bacteria Anthocyanins Antibiotics Antimicrobial Effect Apple Bioavailable C57BL/6 Mouse Calories Cecum Cell Separation Characteristics Chronic Chronic Disease Clinical Clinical Research Collaborations Consumption Coupled Cranberries Data Dependence Deposition Development Diet Dietary Polyphenol Disease Dose Eating Ecology Endotoxemia Energy Metabolism Etiology Event Fat-Restricted Diet Fatty Acids Food Functional disorder Gastrointestinal tract structure Germ-Free Glucose Intolerance Gnotobiotic Grapes Health Health Benefit High Fat Diet Human In Vitro Inflammation Inflammation Mediators Inflammatory disease of the intestine Insulin Resistance Intestines Laboratories Lipopolysaccharides Mediating Metabolic Metabolic Diseases Metabolic syndrome Metagenomics Modeling Mus Non-Insulin-Dependent Diabetes Mellitus Obesity Organ Peripheral Permeability Physiological Physiology Population Proanthocyanidins Reactive Oxygen Species Risk Spices TNF gene Tea Testing Tissues Translating Universities Weight Gain absorption disorder risk epidemiology study experimental study fruits and vegetables glucose tolerance gut microbiome gut microbiota improved inhibitor/antagonist insulin sensitivity intestinal epithelium microbiome microbiota mouse model multidisciplinary nutrition nutritional genomics oral glucose tolerance persistent symptom polyphenol preclinical study prevent public health relevance rRNA Genes resilience response transcriptomics

项目摘要

DESCRIPTION (provided by applicant): This multi-disciplinary and multi-institutional application aims to provide the answer to a key question in human health and nutrition: how do poorly bioavailable dietary polyphenols from fruits and vegetables lower the risk of chronic diseases, such as metabolic syndrome (MetS) and type-2 diabetes (T2D), associated with low-grade chronic inflammation. Using a high fat diet (HFD)-induced metabolic syndrome (MetS) and type-2 diabetes (T2D) murine model coupled with metagenomics and transcriptomics, we will investigate the hypothesis that poorly bioavailable dietary polyphenols from fruits and vegetables act directly in the gastrointestinal (GI) tract to remodel the gut microbiota and reduce local and systemic inflammation via interdependent mechanisms resulting in a reduction in chronic disease risk. While epidemiological, clinical and preclinical studies suggest that consumption of polyphenol-rich foods is associated with reduced risk of MetS and T2D, the mechanism(s) of protection offered by polyphenols has remained elusive due to generally poor polyphenol absorption and distribution to target tissues. Recent studies have shown that consumption of a HFD perturbs gut microbiota ecology and promotes intestinal inflammation, which precedes the development of obesity and insulin resistance characteristic of MetS/T2D. Studies in germ- free (GF; i.e. gnotobiotic) or antibiotic-treated mice demonstrated that consumption of HFD in the absence of gut microbiota protected mice from developing the clinical features of MetS/T2D, implicating the gut microbiota as a key player in the etiology of metabolic diseases. The proposed studies aim to show that poorly bioavailable polyphenols provide resilience to MetS/T2D by changing gut microbiota ecology thus reducing inflammation in the intestine. In collaboration with the laboratory of Dr. Peter Turnbaugh, a leading gut microbiota expert at Harvard University we will: 1) Use the HFD-fed C57BL/6J model of MetS/T2D to test the effects of purified polyphenol fractions from grape and cranberry on microbiome ecology, intestinal inflammation, gut barrier integrity, oral glucose tolerance and adiposity; 2) Study the dose response of polyphenols on gut microbiota and oral glucose tolerance in MetS/T2D mice and test the direct effects of polyphenols on microbiota ecology and physiology in vitro and; 3) Use antibiotic- treated MetS/T2D mice, depleted of their gut microbiota, to test direct polyphenol effects on intestinal inflammation and glucose tolerance in the absence of the gut microbiota. The proposed experiments will evaluate the host physiological and nutrigenomic responses to dietary polyphenols and relate these responses to the changes in host microbiota to provide an integrated mechanistic explanation for the health benefits of polyphenol-rich diets. Successful completion of proposed studies may substantiate the old wisdom that "an apple a day keeps the doctor away."

描述（由申请人提供）：这项多学科和多机构的申请旨在为人类健康和营养中的一个关键问题提供答案：水果和蔬菜中生物利用度差的膳食多酚如何降低慢性疾病的风险，例如代谢综合征 (MetS) 和 2 型糖尿病 (T2D)，与低度慢性炎症相关。使用高脂肪饮食 (HFD) 诱发代谢综合征 (MetS) 和 2 型糖尿病 (T2D)。小鼠模型与宏基因组学和转录组学相结合，我们将研究以下假设：来自水果和蔬菜的生物利用度差的膳食多酚直接作用于胃肠道 (GI)，重塑肠道微生物群并减少流行病学、临床和临床前研究表明，食用富含多酚的食物与降低 MetS 和 T2D 的风险有关，而这种保护机制是通过相互依赖的机制来降低局部和全身炎症的。由于多酚吸收和向目标组织的分布普遍较差，多酚仍然难以捉摸。最近的研究表明，食用高脂饮食会扰乱肠道微生物群生态并促进肠道炎症，从而导致肥胖和肥胖的发生。 MetS/T2D 的胰岛素抵抗特征。在无菌（GF；即无菌）或抗生素治疗的小鼠中进行的研究表明，在缺乏肠道微生物群的情况下食用 HFD 可保护小鼠免受 MetS/T2D 临床特征的发展，这表明肠道微生物群是代谢疾病病因学的关键参与者，拟议的研究旨在表明生物利用度差的多酚通过改变肠道微生物群生态从而减少炎症来提供对 MetS/T2D 的抵抗力。与哈佛大学领先的肠道微生物专家 Peter Turnbaugh 博士的实验室合作，我们将：1) 使用 MetS/T2D 的 HFD 喂养 C57BL/6J 模型来测试来自中的纯化多酚组分的效果。葡萄和蔓越莓对微生物群生态、肠道炎症、肠道屏障完整性、口服葡萄糖耐量和肥胖的影响 2) 研究多酚对肠道微生物群和口服葡萄糖耐量的剂量反应； MetS/T2D 小鼠，并在体外测试多酚对微生物群生态和生理学的直接影响；3) 使用抗生素治疗的 MetS/T2D 小鼠（耗尽其肠道微生物群），测试多酚对肠道炎症和葡萄糖耐量的直接影响。拟议的实验将评估宿主对膳食多酚的生理和营养基因组反应，并将这些反应与宿主微生物群的变化联系起来，为肠道微生物群的变化提供综合的机制解释。富含多酚的饮食对健康的益处成功完成拟议的研究可能会证实“每天一苹果，医生远离我”的古老智慧。