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

该奖项是作为NSF的社会，行为和经济科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，工业或私营部门和政府的科学事业准备有前途的早期职业博士级科学家。SPRF的奖励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。NSF致力于促进来自科学界各部门的科学家，包括来自代表性不足的群体的科学家参与其研究计划和活动;博士后期间被认为是实现这一目标的专业发展的重要水平。每个博士后研究员必须解决推进各自学科领域的重要科学问题。在耶鲁大学Richard Bribiescas博士的赞助下，该博士后奖学金支持早期职业科学家调查人类雌激素受体、相关生活方式因素与健康和疾病之间的关系。微生物组研究人员已经发现了一个肠道微生物的子集，创造了“雌激素组”，能够代谢雌激素。在胃肠道中，这些微生物将已标记用于排泄的非活性雌激素转化回活性形式，其随后可被重吸收到循环中（即，回收）。雌激素对生长、心血管和骨骼健康很重要，并与人类的生活史特征有关，如初潮年龄、绝经期和生育能力。然而，高雌激素终生暴露也与雌激素依赖性癌症的风险增加有关。虽然已经描述了雌激素再循环的机制途径，但不同肠道微生物群落代谢和再循环雌激素的能力的变化在人群或个体之间尚未系统地探索。这些雌激素代谢微生物在个体和群体之间的丰度和组成如何变化尚未得到系统的研究。这项研究将使用进化的公共卫生视角来探索全球人群内和人群之间的雌激素组变化。我们的目标是：1）估计人群内和人群之间雌激素再循环能力的全球人类变化，2）鉴定与雌激素组组成和雌激素再循环能力的变化相关的生活方式因素，和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，我们将分析来自许多不同生活方式的人群的公开微生物组序列。我们将比较微生物群落及其推断的雌激素再循环能力与健康，饮食，体育活动，年龄，初潮和绝经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激素组变异的理解，并为未来关于雌激素组在人类健康中的作用的研究和对话提供基础。该奖项反映了NSF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。

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.