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

地中海饮食(MedDiet)预防2型糖尿病(T2D)的好处在 流行病学研究和随机试验，但其潜在的机制还不完全清楚。 初步证据表明，MedDiet与肠道微生物特征有关，有利于降低T2D风险。 肠道微生物区系，通过产生生物活性分子线索(例如，代谢物和细菌 结构组件)，作用于诸如宿主免疫反应和肠道激素的生物系统(例如， 胰升糖素样肽-1)，这是T2D发病机制的基础。此外，香菇中的高多酚含量 MedDiet可能会与肠道微生物群相互作用，发挥其对健康的好处，因为摄入的多酚 主要在结肠中代谢。到目前为止，还没有研究调查肠道的潜在中介作用。 微生物区系与MedDiet和T2D的关联。大多数关于肠道微生物区系的研究都是横断式的。 研究或小型短期试验。为了获得更高级的机制洞察力，结合元基因组学， 元转录组学和代谢组学在综合框架中提供了一个独特的机会来探索 肠道微生物区系的功能。王东博士将由一个包括梅尔博士在内的跨学科团队进行指导 Stampfer，营养和慢性病流行病学专家，Curtis Huttenhower博士，计算机专家 NIH整合人类微生物组计划的PI生物学家Andrew Chan博士，一位胃肠病专家 在种群规模微生物组研究方面的专长，以及在以下方面的专长的免疫学家温迪·加勒特博士 肠道微生物区系的生物学功能。在K99阶段，王博士将利用他在营养学方面的专业知识 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 在西班牙裔人群中挖掘大型多组学数据库。在R00阶段，Dr。 王将对反复收集的粪便进行元基因组和元翻译测序 样本，并预期招募参与者收集问卷数据，血液和尿液样本在 随机对照试验。R00阶段的研究将测试肠道微生物区系是否会改变长时间的 MedDiet和富含多酚的食物对T2D风险的长期影响，并将检查饮食诱导的作用 肠道微生物在调节宿主免疫动态平衡和肠道激素分泌中的变化。研究结果： 拟议的项目将导致新的机制证据的MedDiet的健康益处，这将有 通过提供更有效和精确的T2D预防，对公众健康产生重大影响。所有这些都将 通过使用创新的研究设计和肠道微生物区系的功能图谱 集成的组学和尖端的生物信息学工具。与关键领导一起提供的出色培训机会 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，并使他成为一名成功和 作为一名独立的营养流行病学家，拥有肠道微生物组和综合‘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.