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

地中海饮食（MedDiet）预防2型糖尿病（T2 D）的益处在以下研究中观察到： 流行病学研究和随机试验，但其潜在机制尚未完全了解。 初步证据表明，MedDiet与肠道微生物特征相关，有利于降低T2 D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 结构组分），作用于生物系统如宿主免疫应答和肠激素（例如， 胰高血糖素样肽-1），其是T2 D发病机制的基础。此外，高多酚含量的 MedDiet可能与肠道微生物群相互作用以发挥其健康益处，因为摄入的多酚 大部分在结肠中代谢迄今为止，没有研究调查肠道的潜在介导作用 微生物群在MedDiet与T2 D的关联中。大多数肠道微生物群的研究都是横断面的 研究或短期小型试验。为了获得更先进的机制见解，结合宏基因组学， 综合框架中的元转录组学和代谢组学提供了探索 肠道微生物群的功能。Dong Wang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 生物学家，NIH综合人类微生物组项目的PI，Andrew Chan博士，胃肠病学家， 在人群规模的微生物组研究的专业知识，和温迪博士加勒特，免疫学家的专业知识， 肠道微生物群的生物学功能。在K99阶段，王博士将利用他在营养方面的专业知识， 流行病学和代谢组学，并将在人类微生物组研究，生物信息学和数据方面进行培训 在西班牙裔人群中的大型队列中挖掘大型多组学数据库。在R 00阶段，博士。 Wang将对反复收集的粪便进行鸟枪宏基因组和元转录组测序 样本，并前瞻性招募参与者收集问卷数据，血液和尿液样本， 随机对照试验。R 00阶段的研究将测试肠道微生物群是否会改变长- MedDiet和富含多酚的食物对T2 D风险的长期影响，并将研究饮食诱导的作用。 肠道微生物变化调节宿主免疫稳态和肠道激素分泌。Findings from the 拟议的项目将导致新的机械证据的健康效益的MedDiet，这将有 通过宣传更有效和精确的T2 D预防，对公共卫生产生重大影响。所有这些都将 通过使用创新的研究设计和肠道微生物群的功能分析， 综合组学和尖端生物信息学工具。与主要领导人的出色培训机会 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 将大大提高候选人的技能和能力，并使他成为一个成功的， 作为营养流行病学家的独立职业，拥有肠道微生物组学和综合组学方面的专业知识。

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.