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: 10198917
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10198917
• 关键词: Address; Adherence; Adopted; Adult; Anti-Inflammatory Agents; Area; Bile Acids; Bioinformatics; Biological; 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; Hispanics; 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; Structure; 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.

地中海饮食 (MedDiet) 对预防 2 型糖尿病 (T2D) 的益处在 流行病学研究和随机试验，但其潜在机制尚不完全清楚。 初步证据表明，医疗饮食与肠道微生物特征相​​关，有利于降低 T2D 风险。 肠道微生物群通过产生生物活性分子线索（例如代谢物和细菌） 结构成分），作用于生物系统，例如宿主免疫反应和肠道激素（例如， 胰高血糖素样肽-1）是 T2D 发病机制的基础。此外，其多酚含量也很高。 MedDiet 可能与肠道微生物群相互作用，发挥其健康益处，因为摄入的多酚 迄今为止，尚无研究调查肠道的潜在介导作用。 微生物群与 MedDiet 与 T2D 的关系 大多数肠道微生物群研究都是横断面的。 研究或小型短期试验，结合宏基因组学获得更先进的机制见解， 综合框架中的宏转录组学和代谢组学提供了一个独特的机会来探索 王栋博士将接受包括 Meir 博士在内的跨学科团队的指导。 Stampfer，营养和慢性病流行病学专家，Curtis Huttenhower 博士，计算专家 生物学家，美国国立卫生研究院综合人类微生物组项目的 PI，安德鲁·陈 (Andrew Chan) 博士，一位胃肠病学家 人口规模微生物组研究方面的专业知识，以及免疫学家 Wendy Garrett 博士的专业知识 在 K99 阶段，王博士将巩固他在营养方面的专业知识。 流行病学和代谢组学，并将接受人类微生物组研究、生物信息学和数据方面的培训 在 R00 阶段，Dr. 在西班牙裔人群中挖掘大型多组学数据库。 王将对重复收集的粪便进行鸟枪法宏基因组和宏转录组测序 样本，并前瞻性招募参与者收集问卷数据、血液和尿液样本 R00 期研究将测试肠道微生物群是否会改变长期肠道菌群。 医学饮食和富含多酚的食物对 T2D 风险的长期影响，并将研究饮食诱发的作用 肠道微生物在调节宿主免疫稳态和肠道激素分泌方面的变化。 拟议的项目将带来有关 MedDiet 健康益处的新机制证据，这将 通过更有效、更精确地预防 T2D，对公共卫生产生重大影响。 通过使用创新的研究设计和肠道微生物群的功能分析来实现 集成的组学和尖端生物信息学工具。与关键领导者的出色培训机会。 研究领域包括肠道微生物组、生物信息学、转化研究和营养干预 将极大地提高候选人的技能和能力，并使他能够获得成功和成功 作为营养流行病学家的独立职业，拥有肠道微生物组和综合“组学”方面的专业知识。