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

Brittain, Rebecca Shae Anna, West Olive MI

Investigators

Abstract

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.