Mechanisms linking dietary fiber, the microbiome, and satiety

项目概要/摘要 该项目支持Katherene Anguah博士的职业发展，使她成为一名 专注于饮食成分如何有益于心脏代谢的独立翻译研究员 通过控制食欲保持健康。指导计划以以前的培训为基础， 技术，学术和专业发展技能，以促进研究的独立性。一个 导师的跨学科团队包括人类临床喂养研究，功能磁 共振成像、微生物组分析和稳定同位素标记的靶向代谢组学。5年 计划包括通过教学指导和旨在提高 扩大研究管理和科学写作的技能。理由：强有力的证据支持 高纤维（HiFi）饮食（如豆类，坚果，蔬菜）与慢性病风险降低之间的关联 心血管疾病（CVD）、2型糖尿病和某些形式的癌症等疾病。但 目前美国膳食纤维的平均消费量为17克/天，明显低于建议水平。 女性25 g/d，男性38 g/d。此外，纤维发酵生产短链脂肪酸 酸（SCFA）产品和微生物组成和活性的改变可能是连接微生物的机制。 HiFi饮食改善健康。重要的是，大部分数据，包括支持 SCFA来源于动物研究。现在需要对人类进行研究， 了解啮齿类动物研究的转化意义和纤维对 微生物代谢物和心脏代谢健康，葡萄糖调节，食欲和饱腹感。中央 一种假说是膳食纤维提供代谢益处的机制包括直接的 上消化道的物理作用，以减缓营养吸收，并间接影响，以减少 通过SCFA诱导的肠激素分泌介导的食物摄入，导致饱腹感增加。 设计：使用豌豆纤维，目标1将测试HiFi饮食对食欲，饱腹感和食欲的影响。 心脏代谢健康以及SCFA浓度升高是否介导饱腹感的改善。目标2将 定量HiFi喂养期间微生物组成和结肠SCFA产生速率的变化， 是否有任何变化是观察到的饱腹感和心脏代谢风险获益的潜在介质 因素相关性：这些研究将大大扩展对机制的理解， 膳食纤维改善人类的饱腹感和心脏代谢健康。

PROJECT SUMMARY/ABSTRACT This project supports the career development of Dr. Katherene Anguah in her path to become an independent translational researcher focusing on how dietary components may benefit cardiometabolic health through the control of appetite. The mentored plan builds on previous training by providing additional technical, academic, and professional development skills to facilitate research independence. An interdisciplinary team of mentors includes experts in human clinical feeding studies, functional magnetic resonance imaging, microbiome analysis, and stable isotope labeled, targeted metabolomics. The 5-year plan includes the opportunity to advance through both didactic instruction and experiences aimed at expanding skills in research management and scientific writing. Rationale: Strong evidence supports the association between high fiber (HiFi) diets (e.g. legumes, nuts, vegetables) and a reduced risk for chronic conditions such as cardiovascular disease (CVD), type 2 diabetes and some forms of cancer. However, the current U.S. average consumption of dietary fiber of 17g/day is significantly below the recommendation level of 25g/d for women and 38g/d for men. Furthermore, fiber fermentation to produce short chain fatty acid (SCFA) products and alterations in microbial composition and activity may be mechanisms linking a HiFi diet to improved health. Importantly, much of the data, including findings supporting a beneficial role of SCFA have been derived from animal studies. Human studies are now needed to advance the understanding of the translational significance of rodent studies and the potential benefit of fiber on microbial metabolites and cardiometabolic health, glucose regulation, appetite and satiety. The central hypothesis is that that the mechanisms by which dietary fiber provides metabolic benefit include direct physical effects in the upper gastrointestinal tract to slow nutrient absorption, and indirect effects to reduce food intake mediated by SCFA-induced secretion of intestinal hormones resulting in increased satiety. Design: Using fiber derived from peas, Aim 1 will test the effect of a HiFi diet on appetite, satiety, and cardiometabolic health and whether elevated SCFA concentration mediates improved satiety. Aim 2 will quantitate the changes in microbial composition and colonic SCFA production rate during HiFi feeding and whether any changes are potential mediators of observed benefits on satiety and cardiometabolic risk factors. Relevance: These studies will significantly expand the understanding of mechanisms by which dietary fiber improves satiety and cardiometabolic health in humans.