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: 8825134
• 负责人: ILYA RASKIN
• 金额: $ 42.14万
• 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/8825134
• 关键词: 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; Epidemiologic Studies; Etiology; Event; Fat-Restricted Diet; Fatty Acids; Fatty acid glycerol esters; Food; Functional disorder; Gastrointestinal tract structure; Germ-Free; Glucose Intolerance; Gnotobiotic; Grapes; Health; Health Benefit; 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; Symptoms; TNF gene; Tea; Testing; Tissues; Translating; Universities; Weight Gain; absorption; dietary supplements; disorder risk; feeding; fruits and vegetables; glucose tolerance; gut microbiota; improved; inhibitor/antagonist; insulin sensitivity; intestinal epithelium; microbiome; nutrition; nutritional genomics; oral glucose tolerance; polyphenol; preclinical study; prevent; public health relevance; rRNA Genes; research study; 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（由申请人提供）：这项多学科、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与低度慢性炎症相关的慢性疾病的风险，例如代谢综合征 (MetS) 和 2 型糖尿病 (T2D)。使用高脂肪饮食 (HFD) 诱导的代谢综合征 (MetS) 和 2 型糖尿病 (T2D) 小鼠模型，结合宏基因组学和转录组学，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 局部和全身炎症通过相互依赖的机制导致慢性病风险降低。虽然流行病学、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 的风险相关，但由于多酚吸收和向目标组织的分布普遍较差，多酚提供的保护机制仍然难以捉摸。最近的研究表明，食用 HFD 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 MetS/T2D 特征的胰岛素抵抗的发生。对无菌（GF；即无菌）或抗生素治疗小鼠的研究表明，在缺乏肠道微生物群的情况下食用 HFD 可保护小鼠免于出现 MetS/T2D 的临床特征，这表明肠道微生物群是代谢疾病病因学中的关键因素。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，从而减少肠道炎症，从而提供对 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 模型来测试从葡萄和蔓越莓中纯化的多酚组分对微生物组生态、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MetS/T2D小鼠肠道菌群和口服葡萄糖耐量的剂量反应，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（肠道微生物群已耗尽），在缺乏肠道微生物群的情况下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，为富含多酚饮食的健康益处提供综合的机制解释。成功完成拟议的研究可能会证实“一天一苹果，医生远离我”的古老智慧。