Abstract
BackgroundEmerging 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.MethodsWe 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.ResultsWe 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).ConclusionsOur data suggest the vaginal microbiota plays an important aetiological role in euploid miscarriage and may represent a target to modify risk of pregnancy loss.
Highlights
Emerging evidence supports an association between vaginal microbiota composition and risk of miscarriage; the underlying mechanisms are poorly understood
The final study cohort consisted of two patient groups, one miscarriage group for which vaginal microbiota, cytogenetic and vaginal cytokine concentrations were available for all cases and one term pregnancy group for which 74 microbiota data and 73 cytokine data were available
Consistent with previous findings in pregnant [18] and nonpregnant women [48, 49], we found that proinflammatory cytokines IL-1β, IL-6 and tumour necrosis factor (TNF)-α were elevated in women with Lactobacillus spp. depleted vaginal microbiome groups (VMG)
Summary
Emerging evidence supports an association between vaginal microbiota composition and risk of miscarriage; 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. Infection is Pregnancy has a unique and dynamic immunological milieu that is required to support a healthy pregnancy [4]. A pro-inflammatory state is required for implantation which involves a release of inflammatory. Chlamydial infection has been shown to cause dysregulation of decidualisation [7], which can contribute to miscarriage by impairing implantation and trophoblast invasion. There is broadly resolution of inflammation until close to term, a pro-inflammatory state returns and contributes to the mechanisms of the onset of labour [8]. Failed tolerance in certain women at the maternal fetal interface and inappropriate, premature activation of inflammation in the reproductive tract may lead to miscarriage or preterm birth [10]
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