Identification of Vaginal Microbial Communities Associated with Extreme Cervical Shortening in Pregnant Women.

Monica Di Paola,Michele Tanturli,Astrid Parenti,Maria Gabriella Torcia,Carlotta Linari,Mariarosaria Di Tommaso,Sara Paccosi,Viola Seravalli,Carlotta De Filippo,Francesco Vitali

doi:10.3390/jcm9113621

Abstract

The vaginal microbiota plays a critical role in pregnancy. Bacteria from Lactobacillus spp. are thought to maintain immune homeostasis and modulate the inflammatory responses against pathogens implicated in cervical shortening, one of the risk factors for spontaneous preterm birth. We studied vaginal microbiota in 46 pregnant women of predominantly Caucasian ethnicity diagnosed with short cervix (<25 mm), and identified microbial communities associated with extreme cervical shortening (≤10 mm). Vaginal microbiota was defined by 16S rRNA gene sequencing and clustered into community state types (CSTs), based on dominance or depletion of Lactobacillus spp. No correlation between CSTs distribution and maternal age or gestational age was revealed. CST-IV, dominated by aerobic and anaerobic bacteria different than Lactobacilli, was associated with extreme cervical shortening (odds ratio (OR) = 15.0, 95% confidence interval (CI) = 1.56–14.21; p = 0.019). CST-III (L. iners-dominated) was also associated with extreme cervical shortening (OR = 6.4, 95% CI = 1.32–31.03; p = 0.02). Gestational diabetes mellitus (GDM) was diagnosed in 10/46 women. Bacterial richness was significantly higher in women experiencing this metabolic disorder, but no association with cervical shortening was revealed by statistical analysis. Our study confirms that Lactobacillus-depleted microbiota is significantly associated with an extremely short cervix in women of predominantly Caucasian ethnicity, and also suggests an association between L. iners-dominated microbiota (CST III) and cervical shortening.

Highlights

The uterine cervix acts as a physical and immune barrier against pathogens’ passage into the uterine cavity during pregnancy
Microbiota analysis of vaginal fluids was performed in a selected cohort of pregnant women with cervical shortening during the second or early third trimester of pregnancy, to identify vaginal communities associated with “extreme” cervical shortening (1–10 mm), a high-risk factor for spontaneous preterm birth [1,2,3]
Iams et al [1] reported that the relative risk of PTB increased as the length of the cervix decreased: they observed that the RR for PTB was 9.49 for lengths at or below the 5th percentile at 24 weeks (22 mm), and 13.99 for lengths at or below the 1st percentile (13 mm), compared with those above the 75th percentile

Summary

Introduction

The uterine cervix acts as a physical and immune barrier against pathogens’ passage into the uterine cavity during pregnancy. In addition to congenital disorders [5], genetic syndromes (e.g., Ehlers–Danlos syndrome) [6] and progesterone deficiency [7], local inflammation secondary to changes in the cervico-vaginal microbiome is another mechanism that has been proposed to cause cervical shortening [8]. Vaginal microbial communities are largely involved in preventing ascending infections from the vagina into the uterine cavity by pathogens that can seriously compromise pregnancy [9,10]. Four CSTs are dominated by Lactobacillus species, better adapted to the vaginal environment [11]. Each species contributes to the first-line defense against bacterial, fungal, and viral pathogens through the release of antimicrobial and anti-inflammatory products and the production of lactic acid that maintains a low vaginal pH [10,12]

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