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.

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.

Citation

Grewal, K., Lee, Y. S., Smith, A., Brosens, J. J., Bourne, T., Al-Memar, M., …Bennett, P. R. (2021). Chromosomally normal miscarriage is associated with vaginal dysbiosis and local inflammation. BMC Medicine, 20(1), Article 38. https://doi.org/10.1186/s12916-021-02227-7

• 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