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Chromosomally normal miscarriage is associated with vaginal dysbiosis and local inflammation

Grewal, Karen; Lee, Yun S.; Smith, Ann; Brosens, Jan J.; Bourne, Tom; Al-Memar, Maya; Kundu, Samit; MacIntyre, David A.; Bennett, Phillip R.

Chromosomally normal miscarriage is associated with vaginal dysbiosis and local inflammation Thumbnail


Authors

Karen Grewal

Yun S. Lee

Ann Smith

Jan J. Brosens

Tom Bourne

Maya Al-Memar

Samit Kundu

David A. MacIntyre

Phillip R. Bennett



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.

Journal Article Type Article
Acceptance Date Dec 1, 2021
Online Publication Date Jan 28, 2022
Publication Date Dec 22, 2021
Deposit Date Jun 16, 2022
Publicly Available Date Jun 17, 2022
Journal BMC Medicine
Electronic ISSN 1741-7015
Publisher BioMed Central
Peer Reviewed Peer Reviewed
Volume 20
Issue 1
Article Number 38
DOI https://doi.org/10.1186/s12916-021-02227-7
Keywords miscarriage; vaginal dysbiosis; local inflammation; inflammation
Public URL https://uwe-repository.worktribe.com/output/9567217
Publisher URL https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-02227-7

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Copyright Statement
© The Author(s). 2022 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License,which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate ifchanges were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commonslicence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtainpermission directly from the copyright holder. To view a copy of this licence, visithttp://creativecommons.org/licenses/by/4.0/.The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to thedata made available in this article, unless otherwise stated in a credit line to the data.





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