Cervicovaginal mucus barrier properties during pregnancy are impacted by the vaginal microbiome

Hannah C Zierden; Kevin DeLong; Fareeha Zulfiqar; Jairo Ortiz Ortiz; Victoria Laney; Sabrine Bensouda; Nicole Hernández; Thuy M Hoang; Samuel K Lai; Justin Hanes; Anne E Burke; Laura M Ensign

doi:10.3389/fcimb.2023.1015625

Cervicovaginal mucus barrier properties during pregnancy are impacted by the vaginal microbiome

Front Cell Infect Microbiol. 2023 Mar 31:13:1015625. doi: 10.3389/fcimb.2023.1015625. eCollection 2023.

Authors

Hannah C Zierden^{1

2}, Kevin DeLong^{1

3}, Fareeha Zulfiqar^{1

3}, Jairo Ortiz Ortiz^{1

3}, Victoria Laney^{1

2}, Sabrine Bensouda^{1

3}, Nicole Hernández^{1

2}, Thuy M Hoang^{1

4}, Samuel K Lai⁵, Justin Hanes^{1

2

3

4

6}, Anne E Burke⁷, Laura M Ensign^{1

2

3

4

6

7}

Affiliations

¹ Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
² Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, United States.
³ Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
⁴ Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
⁵ Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina/North Carolina State University (UNC/NCSU) Joint Department of Biomedical Engineering, Department of Microbiology & Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC, United States.
⁶ Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States.
⁷ Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Abstract

Introduction: Mucus in the female reproductive tract acts as a barrier that traps and eliminates pathogens and foreign particles via steric and adhesive interactions. During pregnancy, mucus protects the uterine environment from ascension of pathogens and bacteria from the vagina into the uterus, a potential contributor to intrauterine inflammation and preterm birth. As recent work has demonstrated the benefit of vaginal drug delivery in treating women's health indications, we sought to define the barrier properties of human cervicovaginal mucus (CVM) during pregnancy to inform the design of vaginally delivered therapeutics during pregnancy.

Methods: CVM samples were self-collected by pregnant participants over the course of pregnancy, and barrier properties were quantified using multiple particle tracking. 16S rRNA gene sequencing was performed to analyze the composition of the vaginal microbiome.

Results: Participant demographics differed between term delivery and preterm delivery cohorts, with Black or African American participants being significantly more likely to delivery prematurely. We observed that vaginal microbiota is most predictive of CVM barrier properties and of timing of parturition. Lactobacillus crispatus dominated CVM samples showed increased barrier properties compared to polymicrobial CVM samples.

Discussion: This work informs our understanding of how infections occur during pregnancy, and directs the engineering of targeted drug treatments for indications during pregnancy.

Keywords: drug delivery; mucus; pregnancy; preterm birth (PTB); vaginal microbiome.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural

MeSH terms

Female
Humans
Infant, Newborn
Microbiota* / genetics
Mucus
Pregnancy
Premature Birth*
RNA, Ribosomal, 16S / genetics
Vagina / microbiology

Substances

RNA, Ribosomal, 16S

Grants and funding

The work was primarily supported by the Burroughs Wellcome Preterm Birth Initiative, grant 1015020, and NIH R01HD103124 awarded to LE. HZ was supported by an NSF GRFP Fellowship (DGE-1746891). KD was supported by a Hartwell Foundation Postdoctoral Fellowship.