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（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：来自水果和蔬菜的生物利用度低的膳食多酚如何降低慢性疾病的风险，如代谢综合征（MetS）和2型糖尿病（T2 D），与低度慢性炎症相关。使用高脂饮食（HFD）诱导的代谢综合征（MetS）和2型糖尿病（T2 D）小鼠模型，结合宏基因组学和转录组学，我们将研究来自水果和蔬菜的生物可利用性差的膳食多酚直接在胃肠道（GI）中作用以重塑肠道微生物群并减少代谢综合征的假设。 局部和全身炎症通过相互依赖的机制，导致慢性疾病的风险降低。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T2 D的风险有关，但多酚提供的保护机制仍然难以捉摸，因为多酚对靶组织的吸收和分布通常较差。最近的研究表明，HFD的消耗扰乱肠道微生物群生态并促进肠道炎症，这先于MetS/T2 D的肥胖和胰岛素抵抗特征的发展。在无菌（GF;即无菌的）或经抗生素处理的小鼠中的研究证明，在不存在肠道微生物群的情况下食用HFD保护小鼠免于发展MetS/T2 D的临床特征，这暗示肠道微生物群是代谢疾病的病因学中的关键参与者。拟议的研究旨在表明，生物利用度低的多酚通过改变肠道微生物群生态，从而减少肠道炎症，从而为MetS/T2 D提供弹性。与哈佛大学肠道微生物群专家Peter Turnbaugh博士的实验室合作，我们将：1）使用HFD喂养的MetS/T2 D的C57 BL/6 J模型来测试来自葡萄和蔓越莓的纯化多酚级分对微生物群生态、肠道炎症、肠道屏障完整性、口服葡萄糖耐受性和肥胖的影响; 2）研究多酚对MetS/T2 D小鼠肠道微生物群和口服葡萄糖耐量的剂量响应，并在体外测试多酚对微生物群生态学和生理学的直接影响; 3）使用抗生素处理的MetS/T2 D小鼠，耗尽它们的肠道微生物群，以测试在不存在肠道微生物群的情况下多酚对肠道炎症和葡萄糖耐量的直接作用。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，为富含多酚的饮食的健康益处提供综合的机制解释。成功地完成拟议的研究可能会证实古老的智慧，“一天一个苹果，医生远离我。"