Doctoral Dissertation Research: Impacts of dietary fat type on energy gain in the human holobiont

人体代谢的营养和能量模型假设所有膳食脂肪具有相同的热值。然而，肠道微生物组研究的最新进展挑战了这一观点，肠道微生物群落随着不同的富含脂肪的饮食而发生变化，由此产生的肠道微生物群对能量增加的影响也不同。本论文项目将从人类全息生物学的角度研究膳食脂肪类型对能量增加的作用，从不同的膳食脂肪来源中获取能量的宿主和微生物机制。通过评估膳食脂肪类型对宿主-微生物相互作用的影响，研究人员旨在更好地了解祖先和现代人类膳食脂肪代谢过程，挑战脂肪等热量性质的传统模型，并深入了解工业人群膳食脂肪摄入与代谢性疾病发病率增加之间的关系。除了为同行评议的科学文献做出贡献外，这项研究还将促进本科生的研究机会，特别是为目前占实验室研究人员80%的女性和科学领域代表性不足的少数群体提供研究机会。此外，通过与哈佛大学陈曾熙公共卫生学院（Harvard T.H. Chan School of Public Health）和哈佛大学科学与文化博物馆（Harvard museum of Science and Culture）的联系，研究人员承诺为让广大公众能够接触到科学的项目做出贡献。人类肠道中数以万亿计的微生物现在被认为在消化和能量调节中发挥着重要作用。然而，迄今为止，过去和现在的人类能量预算模型并没有考虑微生物对从饮食中获取的能量的贡献。在本研究中，研究人员将探索涉及宿主和微生物过程的膳食脂肪代谢机制，评估不同膳食脂肪对宿主能量收支、肠道脂肪吸收和炎症、肠道微生物组成的影响，以及肠道微生物对宿主能量状态的直接贡献。为了解决这些过程，研究人员将使用常规和无菌小鼠模型，这些模型通常用于研究微生物群落变化对人体生理的影响。这项研究将阐明不同膳食脂肪在人类能量代谢进化中所起的作用，并将为针对工业化世界中肥胖、II型糖尿病和其他代谢疾病的高发病率和不断上升的发病率提供新的途径。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Nutritional and energetic models of human metabolism assume that all dietary fats have the same caloric value. However, recent developments in gut microbiome research have challenged this view, with gut microbial communities shifting in response to different fat-rich diets, and the resulting gut microbiota differentially impacting energy gain. This dissertation project will examine the role of dietary fat types on energy gain from a human holobiont perspective, which interrogates both host and microbial mechanisms of energy harvest from different dietary fat sources. By assessing the impact of dietary fat type on host-microbial interactions, the investigators aim to better understand the process of dietary fat metabolism in ancestral and modern humans, to challenge traditional models of the isocaloric nature of fats, and to gain insight into associations between dietary fat intake and increasing rates of metabolic disease in industrial populations. Apart from contributing to the peer-reviewed scientific literature, this research will facilitate undergraduate research opportunities, particularly for women and underrepresented minorities in science, who presently comprise 80% of the laboratory research staff. In addition, through connections with the Harvard T.H. Chan School of Public Health and the Harvard Museums of Science and Culture, the investigators have committed to contributing to programs that make science accessible for a broad public audience. The trillions of microbes that reside in the human gut are now understood to play important roles in digestion and energy regulation. However, to date, models of past and present human energy budgets have not considered the microbial contributions to energy harvested from diet. In this research, the investigators will probe mechanisms of dietary fat metabolism that involve both host and microbial processes, evaluating the impacts of different dietary fats on host energy budget, intestinal fat absorption and inflammation, gut microbial composition, and direct gut microbial contributions to host energy status. To address these processes, the investigators will use conventional and germ-free murine models, which are routinely used for studying the effects of microbial community shifts on human physiology. This research will clarify the role that different dietary fats have played in the evolution of human energy metabolism, and will suggest new pathways for targeting the high and rising rates of obesity, type II diabetes, and other metabolic diseases in the industrialized world.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.