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

• 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
• 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

 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（应用程序提供）：这种多学科和多机构的应用旨在为人类健康和营养的关键问题提供答案：如何从水果和蔬菜中降低慢性疾病风险的可生物可利用的饮食多酚可降低慢性疾病的风险，例如与代谢综合征（Mets）和2型糖尿病（T22D）相关的慢性疾病。 Using a high fat diet (HFD)-induced metabolic syndrome (MetS) and type-2 diabeteses (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 通过相互依存机制的局部和全身性炎症导致慢性疾病风险降低。虽然流行病学，临床和临床前研究表明，多酚食品的消耗与MetS和T2D的风险降低有关，但由于多酚吸收和分布到目标时机，多酚提供的保护机制通常仍然难以捉摸。最近的研究表明，HFD的消费肠道肠道菌群生态学并促进肠道炎症，这是MetS/T2D的肥胖和胰岛素抵抗特征的发展。对无菌种的研究（GF； gf; I.E. gnotobirotic）或抗生素处理的小鼠表明，在没有肠道菌群保护的小鼠的情况下，HFD的消耗ha不受METS/T2D的临床特征，这暗示着肠内菌群的临床特征是代谢性疾病的病因学的关键人物。拟议的研究旨在表明，可生物利用的多酚通过改变肠道微生物群生态学，从而减少肠道感染，从而为Mets/T2D提供弹性。在哈佛大学领先的肠道菌群专家彼得·特恩博（Peter Turnbaugh）的实验室合作：1）使用MetS/T2D的HFD喂养的C57BL/6J模型来测试来自葡萄和蔓越莓对微生物组生态学的纯化多酚馏分对微生物生态学，肠炎症，肠道脑的整合性，或者gluc gluc and的影响2）研究多酚对MetS/T2D小鼠中肠道菌群和口服葡萄糖耐量的剂量反应，并测试多酚对体外微生物群生态学和生理学的直接影响； 3）使用抗生素治疗的MetS/T2D小鼠，加深了肠道微生物群，在没有肠道微生物群的情况下测试直接多酚对肠炎和葡萄糖耐受的影响。提出的实验将评估宿主对饮食多酚的物理和营养素反应，并将这些反应与宿主微生物群的变化相关联，以提供综合的机械解释，以提供富含多酚饮食的健康益处。成功完成拟议的研究可能会证实“每天苹果将医生远离的苹果”的旧智慧。