Impact of Pregnancy Microbiomes on Maternal and Child Cardiovascular Health in a Racially and Ethnically Diverse Cohort

Cardiovascular disease (CVD) is the leading cause of death in U.S. women. Hypertensive disorders of pregnancy greatly increase risk for developing CVD later in life for both mothers and children. Hypertensive disorders of pregnancy affect 16% of pregnancies, and are more prevalent among pregnant people of color, highlighting the need for a health-equitable approach to understanding etiology and prevention/treatment. The human microbiome is a compelling target for etiologic investigations of hypertensive disorders of pregnancy because, unlike the human genome, it can be modified. Cross-sectional studies, case-control studies, and murine models suggest oral, gut, and vaginal microbes can cause cardiovascular diseases, including hypertensive disorders in pregnancy, through their production metabolites. However, previous human studies have not integrated and jointly assessed the oral, gut, and vaginal microbiomes in pregnancy; have not concomitantly examined the role of microbe-dependent targeted and untargeted metabolites; have been limited to a single time point in pregnancy; and have been in populations that lack racial and ethnic diversity. To address these gaps, we will conduct an ancillary study to an ongoing NIH-funded cohort to investigate the associations of maternal microbiomes and metabolomes with hypertensive disorders of pregnancy and maternal child CVD risk factors. Key objectives are to: (1) characterize the distinct body-site specific microbiomes (oral, gut, vaginal) and metabolomes of pregnant persons in a racially and ethnically diverse population, and (2) determine the relative importance of different microbiome niches, microbiome features within these niches, and critical windows for possible intervention to reduce hypertensive disorders of pregnancy and future CVD risk for mothers and their offspring. In particular, we propose to perform whole genome shotgun metagenomics, targeted quantification of short chain fatty acids, trimethylamine N-oxide, and nitrite and nitrate, along with untargeted metabolomics for discovery. We will jointly investigate the microbiomes and metabolomes measured during the 1st/2nd and 3rd trimesters in pregnancy. Drs. Mueller (contact MPI) and Moore (MPI) will carry out this research with an outstanding group of interdisciplinary co-investigators in the collaborative and eminent environments of the University of Colorado Anschutz Medical Campus. Dr. Mueller and Moore’s co-investigators have complementary expertise in statistics (Zhao), -omics analyses (Perng), computational biology and informatics (Olm), body composition and cardiometabolic diseases (Tilves), and community-based dissemination (Rinehart). With the support of their research team, Drs. Mueller and Moore are well positioned to complete the proposed activities. The findings have great potential to: (a) identify early predictors of hypertensive disorders in pregnancy that can be targeted for prevention, (b) reveal novel mechanisms of these hypertensive disorders, (c) offer new disease prevention strategies and therapeutic possibilities, and (d) inform use of the microbiome-metabolome nexus for precision nutrition/medicine. Project Number: 1R01HL176997-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: NOEL MUELLER (+1 co-PI) | Institution: UNIVERSITY OF COLORADO DENVER, Aurora, CO | Award Amount: $720,399 | Activity Code: R01 | Study Section: Reproductive, Perinatal and Pediatric Health Study Section[RPPH] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01HL17699701A1