Association between Pregestational Vaginal Dysbiosis and Incident Hypertensive Disorders of Pregnancy Risk: a Nested Case-Control Study

ABSTRACT A balanced vaginal microbiome dominated by Lactobacillus can help promote women’s reproductive health, with Lactobacillus crispatus showing the most beneficial effect. However, the potential role of vaginal microbiomes in hypertensive disorders of pregnancy (HDP) development is not thorough...

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Main Authors: Xiao Li, Zhaomei Tian, Ran Cui, Jiale Lv, Xin Yang, Lang Qin, Zheng Liu, Changlong Zhang, Congcong Jin, Yanqi Xu, Zi-Jiang Chen, Han Zhao, Shigang Zhao
Format: Article
Language:English
Published: American Society for Microbiology 2023-06-01
Series:mSphere
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/msphere.00096-23
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author Xiao Li
Zhaomei Tian
Ran Cui
Jiale Lv
Xin Yang
Lang Qin
Zheng Liu
Changlong Zhang
Congcong Jin
Yanqi Xu
Zi-Jiang Chen
Han Zhao
Shigang Zhao
author_facet Xiao Li
Zhaomei Tian
Ran Cui
Jiale Lv
Xin Yang
Lang Qin
Zheng Liu
Changlong Zhang
Congcong Jin
Yanqi Xu
Zi-Jiang Chen
Han Zhao
Shigang Zhao
author_sort Xiao Li
collection DOAJ
description ABSTRACT A balanced vaginal microbiome dominated by Lactobacillus can help promote women’s reproductive health, with Lactobacillus crispatus showing the most beneficial effect. However, the potential role of vaginal microbiomes in hypertensive disorders of pregnancy (HDP) development is not thoroughly explored. In this nested case-control study based on an assisted reproductive technology follow-up cohort, we prospectively assessed the association between pregestational vaginal microbiomes with HDP by collecting vaginal swabs from 75 HDP cases (HDP group) and 150 controls (NP group) and using 16S amplicon sequencing for bacterial identification. The vaginal microbial composition of the HDP group significantly differed from that of the NP group. The abundance of L. crispatus was significantly lower, and the abundances of Gardnerella vaginalis was significantly higher, in the HDP group than in the NP group. Of note, L. crispatus-dominated vaginal community state type was associated with a decreased risk for HDP (odds ratio = 0.436; 95% confidence interval, 0.229 to 0.831) compared with others. Additionally, network analysis revealed different bacterial interactions with 61 and 57 exclusive edges in the NP and HDP groups, respectively. Compared with the HDP group, the NP group showed a higher weighted degree and closeness centrality. Several taxa, including G. vaginalis, L. iners, and bacterial vaginosis-associated bacteria (Prevotella, Megasphaera, Finegoldia, and Porphyromonas), were identified as “drivers” for network rewiring. Notable alterations of predicted pathways involved in amino acid, cofactor, and vitamin metabolism; membrane transport; and bacterial toxins were observed in the HDP group. IMPORTANCE The etiology of HDP remains unclear to date. Effective methods for the individualized prediction and prevention are lacking. Pregestational vaginal dysbiosis precedes the diagnosis of HDP, providing a novel perspective on the etiology of HDP. Early pregnancy is the critical period of placental development, and abnormal placentation initiates HDP development. Thus, disease prevention should be considered before pregnancy. Vaginal microbiome characterization and probiotic interventions before pregnancy are preferred because of their safety and potential for early prevention. This study is the first to prospectively assess associations between pregestational vaginal microbiome and HDP. L. crispatus-dominated vaginal community state type is linked to a reduced risk for HDP. These findings suggest that vaginal microbiome characterization may help identify individuals at high risk for HDP and offer potential targets for the development of novel pregestational intervention methods.
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spelling doaj.art-67a73a5a32f74b8f94bca6f2c2ccea442023-06-22T13:00:23ZengAmerican Society for MicrobiologymSphere2379-50422023-06-018310.1128/msphere.00096-23Association between Pregestational Vaginal Dysbiosis and Incident Hypertensive Disorders of Pregnancy Risk: a Nested Case-Control StudyXiao Li0Zhaomei Tian1Ran Cui2Jiale Lv3Xin Yang4Lang Qin5Zheng Liu6Changlong Zhang7Congcong Jin8Yanqi Xu9Zi-Jiang Chen10Han Zhao11Shigang Zhao12Center for Reproductive Medicine, Shandong University, Jinan, Shandong, ChinaCenter for Reproductive Medicine, Shandong University, Jinan, Shandong, ChinaCenter for Reproductive Medicine, Shandong University, Jinan, Shandong, ChinaCenter for Reproductive Medicine, Shandong University, Jinan, Shandong, ChinaCenter for Reproductive Medicine, Shandong University, Jinan, Shandong, ChinaCenter for Reproductive Medicine, Shandong University, Jinan, Shandong, ChinaCenter for Reproductive Medicine, Shandong University, Jinan, Shandong, ChinaCenter for Reproductive Medicine, Shandong University, Jinan, Shandong, ChinaCenter for Reproductive Medicine, Shandong University, Jinan, Shandong, ChinaCenter for Reproductive Medicine, Shandong University, Jinan, Shandong, ChinaCenter for Reproductive Medicine, Shandong University, Jinan, Shandong, ChinaCenter for Reproductive Medicine, Shandong University, Jinan, Shandong, ChinaCenter for Reproductive Medicine, Shandong University, Jinan, Shandong, ChinaABSTRACT A balanced vaginal microbiome dominated by Lactobacillus can help promote women’s reproductive health, with Lactobacillus crispatus showing the most beneficial effect. However, the potential role of vaginal microbiomes in hypertensive disorders of pregnancy (HDP) development is not thoroughly explored. In this nested case-control study based on an assisted reproductive technology follow-up cohort, we prospectively assessed the association between pregestational vaginal microbiomes with HDP by collecting vaginal swabs from 75 HDP cases (HDP group) and 150 controls (NP group) and using 16S amplicon sequencing for bacterial identification. The vaginal microbial composition of the HDP group significantly differed from that of the NP group. The abundance of L. crispatus was significantly lower, and the abundances of Gardnerella vaginalis was significantly higher, in the HDP group than in the NP group. Of note, L. crispatus-dominated vaginal community state type was associated with a decreased risk for HDP (odds ratio = 0.436; 95% confidence interval, 0.229 to 0.831) compared with others. Additionally, network analysis revealed different bacterial interactions with 61 and 57 exclusive edges in the NP and HDP groups, respectively. Compared with the HDP group, the NP group showed a higher weighted degree and closeness centrality. Several taxa, including G. vaginalis, L. iners, and bacterial vaginosis-associated bacteria (Prevotella, Megasphaera, Finegoldia, and Porphyromonas), were identified as “drivers” for network rewiring. Notable alterations of predicted pathways involved in amino acid, cofactor, and vitamin metabolism; membrane transport; and bacterial toxins were observed in the HDP group. IMPORTANCE The etiology of HDP remains unclear to date. Effective methods for the individualized prediction and prevention are lacking. Pregestational vaginal dysbiosis precedes the diagnosis of HDP, providing a novel perspective on the etiology of HDP. Early pregnancy is the critical period of placental development, and abnormal placentation initiates HDP development. Thus, disease prevention should be considered before pregnancy. Vaginal microbiome characterization and probiotic interventions before pregnancy are preferred because of their safety and potential for early prevention. This study is the first to prospectively assess associations between pregestational vaginal microbiome and HDP. L. crispatus-dominated vaginal community state type is linked to a reduced risk for HDP. These findings suggest that vaginal microbiome characterization may help identify individuals at high risk for HDP and offer potential targets for the development of novel pregestational intervention methods.https://journals.asm.org/doi/10.1128/msphere.00096-23hypertensive disorders of pregnancyvaginamicrobiome16S ribosomal RNALactobacillus crispatus
spellingShingle Xiao Li
Zhaomei Tian
Ran Cui
Jiale Lv
Xin Yang
Lang Qin
Zheng Liu
Changlong Zhang
Congcong Jin
Yanqi Xu
Zi-Jiang Chen
Han Zhao
Shigang Zhao
Association between Pregestational Vaginal Dysbiosis and Incident Hypertensive Disorders of Pregnancy Risk: a Nested Case-Control Study
mSphere
hypertensive disorders of pregnancy
vagina
microbiome
16S ribosomal RNA
Lactobacillus crispatus
title Association between Pregestational Vaginal Dysbiosis and Incident Hypertensive Disorders of Pregnancy Risk: a Nested Case-Control Study
title_full Association between Pregestational Vaginal Dysbiosis and Incident Hypertensive Disorders of Pregnancy Risk: a Nested Case-Control Study
title_fullStr Association between Pregestational Vaginal Dysbiosis and Incident Hypertensive Disorders of Pregnancy Risk: a Nested Case-Control Study
title_full_unstemmed Association between Pregestational Vaginal Dysbiosis and Incident Hypertensive Disorders of Pregnancy Risk: a Nested Case-Control Study
title_short Association between Pregestational Vaginal Dysbiosis and Incident Hypertensive Disorders of Pregnancy Risk: a Nested Case-Control Study
title_sort association between pregestational vaginal dysbiosis and incident hypertensive disorders of pregnancy risk a nested case control study
topic hypertensive disorders of pregnancy
vagina
microbiome
16S ribosomal RNA
Lactobacillus crispatus
url https://journals.asm.org/doi/10.1128/msphere.00096-23
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