Mechanisms linking dietary fiber, the microbiome, and satiety

项目摘要/摘要 该项目支持Katherene Anguah博士的职业发展，使她成为 关注饮食成分如何有益于心脏代谢的独立翻译研究人员 通过控制食欲来保持健康。指导计划以以前的培训为基础，通过提供更多 技术、学术和专业发展技能，以促进研究的独立性。一个 跨学科的导师团队包括人类临床喂养研究、功能磁学 磁共振成像，微生物组分析，稳定同位素标记，靶向代谢组学。五年制 计划包括通过教学指导和经验提高的机会，旨在 拓展研究管理和科学写作方面的技能。理由：强有力的证据支持 高纤维(HiFi)饮食(如豆类、坚果、蔬菜)与降低慢性病风险之间的关系 心血管疾病(CVD)、2型糖尿病和某些形式的癌症。然而， 目前美国人每天平均摄入的膳食纤维为17克，大大低于推荐摄入量 女性25g/d，男性38g/d。此外，纤维发酵生产短链脂肪 酸(SCFA)产物和微生物组成和活性的变化可能是连接 高保真饮食，改善健康。重要的是，许多数据，包括支持的有益作用的发现 SCFA来源于动物研究。现在需要进行人体研究来推进 理解啮齿动物研究的翻译意义和纤维在 微生物代谢产物与心脏代谢健康、葡萄糖调节、食欲和饱腹感。中环 假设膳食纤维提供代谢益处的机制包括直接 物理影响在上消化道减慢养分的吸收，间接影响则减少 食物摄入由SCFA诱导的肠道激素分泌介导，导致饱腹感增加。 设计：使用从豌豆中提取的纤维，目标1将测试高保真饮食对食欲、饱腹感和 心脏代谢健康，以及升高的SCFA浓度是否有助于改善饱腹感。目标2将 定量测定高保真饲喂过程中肠道微生物组成和单链脂肪酸产生率的变化 是否有任何变化是观察到的饱腹感和心脏代谢风险益处的潜在中介 各种因素。相关性：这些研究将显著扩大对以下机制的理解 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.