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Chromosomally normal miscarriage is associated with vaginal dysbiosis and local inflammation

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Grewal, Karen, Lee, Yun S., Smith, Ann, Brosens, Jan J., Bourne, Tom, Al-Memar, Maya, Kundu, Samit, MacIntyre, David A. and Bennett, Phillip R. (2022) Chromosomally normal miscarriage is associated with vaginal dysbiosis and local inflammation. BMC Medicine, 20 (1). 38. doi:10.1186/s12916-021-02227-7 ISSN 1741-7015.

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Official URL: https://doi.org/10.1186/s12916-021-02227-7

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Abstract

Background: Emerging evidence supports an association between vaginal microbiota composition and risk of miscarriage; however, the underlying mechanisms are poorly understood. We aim to investigate the vaginal microbial composition and the local immune response in chromosomally normal and abnormal miscarriages and compare this to uncomplicated pregnancies delivering at term. Methods: We used 16S rRNA gene based metataxonomics to interrogate the vaginal microbiota in a cohort of 167 women, 93 miscarriages (54 euploid and 39 aneuploid using molecular cytogenetics) and 74 women who delivered at term and correlate this with the aneuploidy status of the miscarriages. We also measured the concentrations of IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, IL-1β, IL-18 and IL-10 in cervical vaginal fluid. Results: We show that euploid miscarriage is associated with a significantly higher prevalence of Lactobacillus spp. deplete vaginal microbial communities compared to aneuploid miscarriage (P = 0.01). Integration of matched cervicovaginal fluid immune-profiles showed that Lactobacillus spp. depleted vaginal microbiota associated with pro-inflammatory cytokine levels most strongly in euploid miscarriage compared to viable term pregnancy (IL-1β; P < 0.001, IL-8; P = 0.01, IL-6; P < 0.001). Conclusions: Our data suggest the vaginal microbiota plays an important aetiological role in euploid miscarriage and may represent a target to modify risk of pregnancy loss.

Item Type: Journal Article
Subjects: R Medicine > RG Gynecology and obstetrics
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Miscarriage -- Research, Medical microbiology, Women -- Health and hygiene, Communicable diseases, Pregnancy -- Complications -- Research
Journal or Publication Title: BMC Medicine
Publisher: BioMed Central Ltd.
ISSN: 1741-7015
Official Date: 28 January 2022
Dates:
DateEvent
28 January 2022Published
29 December 2021Accepted
Volume: 20
Number: 1
Article Number: 38
DOI: 10.1186/s12916-021-02227-7
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 22 February 2022
Date of first compliant Open Access: 24 February 2022
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
P62774Tommy's National Centre for Miscarriage ResearchUNSPECIFIED

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