Mediterranean Diet, Polyphenol-Rich Foods, Gut Microbiota and Type 2 Diabetes

地中海饮食、富含多酚的食物、肠道微生物群和 2 型糖尿病

• 批准号: 10457834
• 负责人: Dong Wang
• 金额: $ 24.89万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10457834
• 关键词: Address; Adherence; Adopted; Adult; Anti-Inflammatory Agents; Area; Bile Acids; Bioinformatics; Biological Assay; Biological Markers; Biological Process; Blood; Branched-Chain Amino Acids; Cardiometabolic Disease; Chronic Disease; Cohort Studies; Colon; Cross-Sectional Studies; Cues; Data; Data Collection; Databases; Development; Diabetes Mellitus; Diabetes prevention; Diet; Dietary Intervention; Ensure; Epidemiologist; Epidemiology; Etiology; Food; Gastroenterologist; Health Benefit; Hispanic Community Health Study; Hispanic Populations; Homeostasis; Hormone secretion; Hormones; Human Microbiome; Immune; Immune response; Immunologist; Inflammatory; Ingestion; Intake; Intestinal permeability; Israel; Knowledge; Link; Long-Term Effects; Mediating; Mediterranean Diet; Mentors; Metabolism; Metagenomics; Mining; Molecular; Non-Insulin-Dependent Diabetes Mellitus; Nutritional; Participant; Pathogenesis; Patient Recruitments; Peptide YY; Phase; Plasma; Population; Positioning Attribute; Prevention; Public Health; Questionnaires; Randomized Controlled Trials; Reporting; Research; Research Design; Research Personnel; Resolution; Role; Sampling; Shotguns; Strategic Planning; Study of Latinos; Testing; Training; Translational Research; United States National Institutes of Health; Urine; Work; aminoacid biosynthesis; bioinformatics tool; biological systems; blood glucose regulation; career; cohort; cytokine; data mining; design; diabetes risk; dietary approach; epidemiology study; experience; fasting glucose; follow-up; glucagon-like peptide 1; good diet; gut microbiome; gut microbiota; healthy lifestyle; immune function; improved; individualized prevention; innovation; insight; interest; metabolome; metabolomics; metatranscriptomics; microbial; microbial community; microbiome research; multidisciplinary; multiple omics; novel; nutritional epidemiology; overexpression; polyphenol; prospective; randomized trial; recruit; response; skills; stool sample; success; training opportunity; trimethyloxamine

The benefits of the Mediterranean diet (MedDiet) for type 2 diabetes (T2D) prevention were observed in epidemiologic studies and a randomized trial, yet the underlying mechanisms are not fully understood. Preliminary evidence indicates that a MedDiet is associated with gut microbial features favoring lower T2D risk. The gut microbiota, through producing biologically active molecular cues (e.g., metabolites and bacterial structural components), act on biological systems such as the host immune response and gut hormones (e.g., glucagon-like peptide-1) that underlie the pathogenesis of T2D. In addition, the high-polyphenol content of the MedDiet may interact with the gut microbiota to exert its health benefits because ingested polyphenols are mostly metabolized in the colon. To date, no study has investigated the potential mediating role of the gut microbiota in the association of the MedDiet with T2D. Most studies of the gut microbiota are cross-sectional studies or small short-term trials. For more advanced mechanistic insights, combining metagenomics, metatranscriptomics and metabolomics in an integrated framework presents a unique opportunity to probe the function of gut microbiota. Dr. Dong Wang will be mentored by an interdisciplinary team that includes Dr. Meir Stampfer, an expert in nutritional and chronic disease epidemiology, Dr. Curtis Huttenhower, a computational biologist who is a PI of NIH Integrative Human Microbiome Project, Dr. Andrew Chan, a gastroenterologist with expertise in population-scale microbiome study, and Dr. Wendy Garrett, an immunologist with expertise on biological function of gut microbiota. During the K99 phase, Dr. Wang will build on his expertise in nutritional epidemiology and metabolomics, and will be trained in human microbiome research, bioinformatics, and data mining the large multi-omics databases in a large cohort in Hispanic population. During the R00 phase, Dr. Wang will perform shotgun metagenomic and metatranscriptomic sequencing on repeatedly collected stool samples, and prospectively recruit participants to collect questionnaire data, blood and urine samples in a randomized controlled trial. The R00-phase research will test whether the gut microbiota modifies the long- term effects of the MedDiet and polyphenol-rich foods on T2D risk, and will examine the role of diet-induced gut microbial changes in regulating host immune homeostasis and gut hormone secretion. Findings from the proposed project will lead to novel mechanistic evidence on the health benefits of the MedDiet, which will have substantial public health impact by informing more effective and precision prevention of T2D. All of these will be possible through the use of an innovative study design and the functional profiling of gut microbiota by integrated ‘omics and cutting-edge bioinformatic tools. The outstanding training opportunities with key leaders in research areas including gut microbiome, bioinformatics, translational research and nutritional interventions will greatly enhance the skills and capabilities of the candidate, and position him for a successful and independent career as a nutritional epidemiologist with expertise in gut microbiome and integrated ‘omics.

在 流行病学研究和一项随机试验，但尚未完全了解潜在的机制。 初步证据表明，Meddiet与肠道微生物特征有利于较低的T2D风险。 肠道微生物群，通过产生生物活性分子提示（例如代谢物和细菌 结构成分），对宿主免疫响应和肠激素等生物系统的作用（例如， 胰高血糖素样肽1）是T2D发病机理的基础。此外， Meddiet可能与肠道微生物群相互作用以施加其健康益处，因为摄入的多酚是 大多在结肠中代谢。迄今为止，尚无研究肠道的潜在中介作用 Microbiota与Meddiet与T2D的关联。肠道菌群的大多数研究是横截面 研究或小型短期试验。有关更先进的机械见解，结合宏基因组学， 集成框架中的元文字组和代谢组学为探测独特的机会 肠道菌群的功能。宗博士将由包括Meir博士在内的跨学科团队召集 营养和慢性病流行病学专家Stampfer，计算 生物学家是NIH综合人类微生物组项目的PI，Andrew Chan博士，胃肠病学家 人口规模微生物组研究专业知识，以及具有专业知识的免疫学家Wendy Garrett博士 肠道菌群的生物学功能。在K99阶段，Wang博士将基于他的营养专业知识 流行病学和代谢组学，并将接受人类微生物组研究，生物信息学和数据的培训 在西班牙裔人口中的大型队列中挖掘大型多币数据库。在R00阶段，博士 王将在反复收集的凳子上进行shot弹枪元基因组和元文字测序 样本，并前瞻性地招募参与者收集问卷数据，血液和尿液样本 随机对照试验。 R00相研究将测试肠道微生物群是否修改了长期 Meddiet和多酚食品对T2D风险的期限影响，并将检查饮食引起的作用 肠道微生物在调节宿主免疫稳态和肠horse分泌方面的变化。来自 拟议的项目将导致有关Meddiet健康益处的新机械证据，这将有 通过告知更有效和精确预防T2D的实质性公共卫生影响。所有这些都会 通过使用创新的研究设计和肠道微生物群的功能分析，可以通过 集成的“ OMICS和最先进的生物信息学工具”。与主要领导者的出色培训机会 在研究领域，包括肠道微生物组，生物信息学，翻译研究和营养干预措施 将大大提高候选人的技能和能力，并为成功和 独立职业是肠道微生物组和综合'Omics专家的营养流行病学家。

项目成果

Successful weight regain attenuation by autologous fecal microbiota transplantation is associated with non-core gut microbiota changes during weight loss; randomized controlled trial.

• DOI: 10.1080/19490976.2023.2264457
• 发表时间: 2023-12
• 期刊: Gut microbes
• 影响因子: 12.2

Changes in arginine are inversely associated with type 2 diabetes: A case-cohort study in the PREDIMED trial.

• DOI: 10.1111/dom.13514
• 发表时间: 2019-03
• 期刊: Diabetes, obesity & metabolism
• 作者: Yu E;Ruiz-Canela M;Razquin C;Guasch-Ferré M;Toledo E;Wang DD;Papandreou C;Dennis C;Clish C;Liang L;Bullo M;Corella D;Fitó M;Gutiérrez-Bedmar M;Lapetra J;Estruch R;Ros E;Cofán M;Arós F;Romaguera D;Serra-Majem L;Sorlí JV;Salas-Salvadó J;Hu FB;Martínez-González MA
• 通讯作者: Martínez-González MA

The effects of the Green-Mediterranean diet on cardiometabolic health are linked to gut microbiome modifications: a randomized controlled trial.

• DOI: 10.1186/s13073-022-01015-z
• 发表时间: 2022-03-10
• 期刊: Genome medicine
• 影响因子: 12.3
• 作者: Rinott E;Meir AY;Tsaban G;Zelicha H;Kaplan A;Knights D;Tuohy K;Scholz MU;Koren O;Stampfer MJ;Wang DD;Shai I;Youngster I
• 通讯作者: Youngster I

Dietary Patterns and Precision Prevention of Heart Failure.

饮食模式和心力衰竭的精准预防。

• DOI: 10.1016/j.jacc.2019.02.037
• 发表时间: 2019
• 期刊: Journal of the American College of Cardiology
• 影响因子: 24
• 作者: Wang,DongD