A Human Microbiota-Associated Murine Model for Assessing the Impact of the Vaginal Microbiota on Pregnancy Outcomes

• Type of Material: Article
• Authors: Alexandra A. Wolfarth, Emory University; Taylor M. Smith, Emory University; David VanInsberghe, Emory University; Anne Dunlop, Emory University; Andrew Neish, Emory University; Elizabeth Corwin, Emory University; Rheinallt Jones, Emory University
• Language: English
• Date: 2020-10-06
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Wolfarth, Smith, VanInsberghe, Dunlop, Neish, Corwin and Jones.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fcimb.2020.570025
• Title of Journal or Parent Work: FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
• Volume: 10
• Start Page: 570025
• End Page: 570025
• Grant/Funding Information: This study was supported in part by the Emory Gnotobiotic Animal (EGAC), which is subsidized by the Emory University School of Medicine and is one of the Emory Integrated Core Facilities. Additional support was provided by the Georgia Clinical & Translational Science Alliance of the National Institutes of Health under Award Number UL1TR002378.; This study was supported in part by the Emory University Synergy Program and the National Institutes of Health National Institute of Nursing Research [R01NR014800] and National Institute of Environmental Health Sciences [R24ES029490].
• Keywords: Life Sciences & Biomedicine; BACTERIAL-VAGINOSIS; MICE; PREMATURE; pregnancy; inflammation; vaginal microbiota; AMNIOTIC-FLUID; CHORIOAMNIONITIS; humanization; bacterial vaginosis (BV); Science & Technology; INFECTION; Immunology; EXPRESSION; Microbiology
• Research Categories: Biology, Microbiology; Health Sciences, Immunology; Health Sciences, Obstetrics and Gynecology

Abstract

Disease states are often linked to large scale changes in microbial community structure that obscure the contributions of individual microbes to disease. Establishing a mechanistic understanding of how microbial community structure contribute to certain diseases, however, remains elusive thereby limiting our ability to develop successful microbiome-based therapeutics. Human microbiota-associated (HMA) mice have emerged as a powerful approach for directly testing the influence of microbial communities on host health and disease, with the transfer of disease phenotypes from humans to germ-free recipient mice widely reported. We developed a HMA mouse model of the human vaginal microbiota to interrogate the effects of Bacterial Vaginosis (BV) on pregnancy outcomes. We collected vaginal swabs from 19 pregnant African American women with and without BV (diagnosed per Nugent score) to colonize female germ-free mice and measure its impact on birth outcomes. There was considerable variability in the microbes that colonized each mouse, with no association to the BV status of the microbiota donor. Although some of the women in the study had adverse birth outcomes, the vaginal microbiota was not predictive of adverse birth outcomes in mice. However, elevated levels of pro-inflammatory cytokines in the uterus of HMA mice were detected during pregnancy. Together, these data outline the potential uses and limitations of HMA mice to elucidate the influence of the vaginal microbiota on health and disease.