Postdoctoral Fellowship: SPRF: A Novel Exploration of Global Variation in the Human Estrobolome

该奖项是作为NSF社会、行为和经济学博士后研究奖学金(SPRF)计划的一部分提供的。SPRF计划的目标是为学术界、工业界或私营部门和政府的科学职业生涯培养有前途的、早期职业博士水平的科学家。SPRF奖项包括在知名科学家的赞助下进行两年的培训，并鼓励博士后研究员进行独立研究。国家科学基金会致力于促进科学界所有阶层的科学家参与其研究方案和活动，包括那些来自代表性不足的群体的科学家；博士后阶段被认为是实现这一目标的专业发展的一个重要水平。每个博士后研究员都必须解决推动各自学科领域向前发展的重要科学问题。在耶鲁大学理查德·布里比斯卡斯博士的赞助下，这个博士后奖学金奖支持一位早期职业科学家研究人类雌激素组、相关的生活方式因素以及健康和疾病之间的关系。微生物组研究人员发现了肠道微生物的一个子集，被称为“雌激素组”，能够代谢雌激素。在胃肠道中，这些微生物将标记为要排泄的非活性雌激素转化为活性形式，然后可以重新吸收到循环中(即循环)。雌激素对生长、心血管和骨骼健康很重要，并与人类生活史特征有关，如月经初潮年龄、更年期和生育能力。然而，终生高暴露于雌激素也会增加患雌激素依赖型癌症的风险。虽然雌激素循环的机制已经被描述，但不同肠道微生物群落代谢和循环雌激素的能力在群体或个体之间的差异尚未得到系统的探索。这些雌激素代谢微生物在个体和种群之间的丰度和组成如何变化还没有得到系统的研究。本研究将从进化公共卫生的角度来探索全球种群内和种群之间的雌酚组变异。我们的目标是：1)估计全球人类在种群内和种群之间雌激素回收能力的差异，2)确定与雌激素组分和雌激素回收能力变化相关的生活方式因素，3)探索雌激素组在人类生活史特征、健康、疾病和生物权衡中的潜在作用。在广泛的地理范围内，我们将分析来自不同生活方式的人类种群的公开可用的微生物组序列。我们将比较微生物群落及其推断的雌激素回收能力与健康、饮食、体力活动、年龄、月经初潮和更年期年龄以及雌激素相关疾病的数据。这些结果将促进我们对人类雌酚组变异的理解，并为未来关于雌酚组在人类健康中的作用的研究和对话提供基础。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This award was provided as part of NSF's Social, Behavioral and Economic Sciences Postdoctoral Research Fellowships (SPRF) program. The goal of the SPRF program is to prepare promising, early career doctoral-level scientists for scientific careers in academia, industry or private sector, and government. SPRF awards involve two years of training under the sponsorship of established scientists and encourage Postdoctoral Fellows to perform independent research. NSF seeks to promote the participation of scientists from all segments of the scientific community, including those from underrepresented groups, in its research programs and activities; the postdoctoral period is considered to be an important level of professional development in attaining this goal. Each Postdoctoral Fellow must address important scientific questions that advance their respective disciplinary fields. Under the sponsorship of Dr. Richard Bribiescas at Yale University, this postdoctoral fellowship award supports an early career scientist to investigate the relationship between the human estrobolome, associated lifestyle factors, and health and disease. Microbiome researchers have discovered a subset of gut microbes, coined the “estrobolome,” that are capable of metabolizing estrogens. In the gastrointestinal tract, these microbes convert inactive estrogens that have been marked for excretion back into active form, which can subsequently be reabsorbed into circulation (i.e., recycled). Estrogen is important for growth, cardiovascular and bone health, and is linked to human life history traits such as age at menarche, menopause, and fertility. However, high lifetime exposures to estrogen are also associated with increased risk for estrogen-dependent cancers. While the mechanistic pathway for estrogen recycling has been described, variation in different gut microbial community capacities to metabolize and recycle estrogens has not been systematically explored between populations or individuals. How these estrogen-metabolizing microbes vary in abundance and composition between individuals and populations has not been systematically investigated.This research will use an evolutionary public health perspective to explore estrobolome variation within and between populations globally. Our objectives are to: 1) estimate global human variation in estrogen recycling capacities within and between populations, 2) identify lifestyle factors associated with variation in estrobolome composition and estrogen recycling capacities, and 3) explore the potential role of the estrobolome in human life history traits, health, disease, and biological trade-offs. At a broad geographic scale, we will analyze publicly available microbiome sequences from human populations across many different lifestyles. We will compare microbiome communities and their inferred estrogen recycling capacities with data on health, diet, physical activity, age, ages of menarche and menopause, and estrogen-associated diseases. These results will advance our understanding of human estrobolome variation and provide a basis for future research and conversations about the role of the estrobolome in human health.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.