Association Of Pregnancy Vaginal Microbiome And Adverse Pregnancy Outcomes

Background:The vaginal microbiome is a key component of the reproductive ecosystem and is closely related to the occurrence and progression of numerous reproductive diseases.Lactobacillus from vaginal can produce lactic acid,antibacterial peptides,H2O2 and other substances to maintain a healthy ecosystem with dominant lactobacillus abundance,low species diversity and weakly acidic microenvironment.During pregnancy,decreased abundance of Lactobacillus can cause opportunistic pathogens to ascend through the cervix into the uterine cavity,causing diseases including preterm birth(PTB),premature rupture of membranes(PROM),and neonatal sepsis.Recent studies have suggested that the use of vaginal microbiome allows for early prediction of pregnancy outcomes.However,due to many factors such as regional variation,populational bacterial background and study sample size,the results of the studies were inconsistent or even contradictory.Objectives:The aim of this study was to investigate the correlations between the vaginal microbiome and key adverse pregnancy outcomes based on a clinical cohort of pregnant women in China.Further explore the role of the vaginal microbiota as potential biomarker in the early prediction of adverse pregnancy outcomes(APOs).Methods:Pregnant women who visited NanFang Hospital of Southern Medical University for pregnant cares were recruited at their first visits according to the inclusion exclusion criteria.All the subjects were written questionnaire of medical history,family history,individual life habits and the following up of pregnancy outcomes.Vaginal secretion samples were collected for 16S rRNA sequencing to analyze the microbiome composition,diversities,core different bacterial and Vaginal Microbiome Groups(VMG).Logistic regression,Fisher’s Exact Test,Spearman and other methods were used for statistical analyses.For all statistical tests,significance was based on p<0.05 unless otherwise stated.Results:1.85.98%populations samples had healthy microbiome feature which were dominated by lactobacillus with low alpha diversity.The majorly bacterial by species was Lactobacillus crispatus(39.98%)or Lactobacillus iners(35.98%).2.Lactobacillus crispatus was negatively related with most vaginal bacterial and pathogens(p<0.001).Lactobacillus iners was positively related with Megasphaera spp.,Aerococcus spp.,but negatively with Gardnerella spp.and Atopobium vaginae.3.Leukocytes in vaginal discharge were significantly associated Lactobacillus iners and Streptococcus agalactiae(p<0.001).High sialidase activity group has a significant increased alpha diversity(Shannon Index)compared to the low sialidase activity group(p<0.001).By using LefSe analysis,the result showed that Gardnerella spp.and other anaerobes were significant enrichment in high sialidase activity group(p<0.001).We used logistic regression to evaluate sialidase activity as a biomarker to predict microbiome dysbiosis.The result showed that it has high specificity(99.01%)but low sensitivity(14.08%).4.The association between vaginal microbiome and main adverse pregnancy outcomes.offspring’s birth weight was significant greater of high Body Mass Index(BMI)women than low BMI’s(p<0.001).Also,High BMI pregnant women had increased risk of Gestational Diabetes Mellitus(GDM)compared to normal BMI’s and low BMI’s(p<0.001).Pregnancy women with GDM has significant vaginal lactobacillus deplete in the mid-trimester.Furthermore,to compare the core different bacteria of GDM group and non-GDM group by used LefSe analysis,GDM women was enrichment abundance of Lachnospiraceae and Parvimonas.5.There was no microbiota feature significantly related to Preterm birth,PROM,Chorioamnionitis and other APOs(p>0.05).Conclusion:1.This study illustrated the vaginal microbiome of the mid-trimester of Chinese women almost with healthy microbiome feature which Lactobacillus dominant and low alpha diversity.By species,Lactobacillus crispatus and Lactobacillus iners were the most frequency dominate bacterial.2.Sialidase activity has high specificity for assessing vaginal Lactobacillus depletion,but the sensitivity was low,suggesting that the role of vaginal sialidase activity as a screening biomarker needs to be further investigated.3.With exception of GDM,there is no distinct vaginal microbiota feature of Preterm Birth,PROM,Chorioamnionitis and other APOs.Vaginal microbiota composition was associated with GDM,with significantly lactobacillus deplete and Lachnospiraceae,Parvimonas enrichment,but their causal relationship needs to be demonstrated.4.Lactobacillus crispatus may play a protective role in vaginal ecosystems.Due to a complex associateship of Lactobacillus iners with different other bacteria,suggesting that Lactobacillus iners act as an unclear role driven by the host environment or the interaction with different bacteria.Further in-depth study is needed to address the question.