Vaginal Biomarkers That Predict Cervical Length and Dominant Bacteria in the Vaginal Microbiomes of Pregnant Women

ABSTRACT In many impoverished regions of the world, it may not be possible to assess two major risk factors for preterm birth: a short cervical length and the depletion of vaginal lactobacilli. We determined whether measuring specific compounds in vaginal fluid might be a simple, noninvasive, and co...

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Autores principales:	Steven S. Witkin, Antonio F. Moron, Benjamin J. Ridenhour, Evelyn Minis, Alan Hatanaka, Stephanno G. P. Sarmento, Marcelo S. Franca, Francisco H. C. Carvalho, Tatiana K. Hamamoto, Rosiane Mattar, Ester Sabino, Iara M. Linhares, Marilza V. C. Rudge, Larry J. Forney
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	cervical length d-lactic acid preterm birth TIMP-1 vaginal microbiome Lactobacillus Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/05b6c89f3a3e4d8a80b9c75a9742053a
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spelling	oai:doaj.org-article:05b6c89f3a3e4d8a80b9c75a9742053a2021-11-15T15:59:41ZVaginal Biomarkers That Predict Cervical Length and Dominant Bacteria in the Vaginal Microbiomes of Pregnant Women10.1128/mBio.02242-192150-7511https://doaj.org/article/05b6c89f3a3e4d8a80b9c75a9742053a2019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02242-19https://doaj.org/toc/2150-7511ABSTRACT In many impoverished regions of the world, it may not be possible to assess two major risk factors for preterm birth: a short cervical length and the depletion of vaginal lactobacilli. We determined whether measuring specific compounds in vaginal fluid might be a simple, noninvasive, and cost-effective way to predict the bacteria that dominate the vaginal microbiome and indicate the presence of a shortened cervix (<25 mm). Vaginal fluid samples were prospectively collected from mid-trimester pregnant women, and the concentrations of d- and l-lactic acid, tissue inhibitor of matrix metalloproteinases TIMP-1 and TIMP-2, matrix metalloproteinases MMP-2 and MMP-8, the 70-kDa heat shock protein, a2 isoform of vacuolar ATPase, and sequestrome-1 were quantified by an enzyme-linked immunosorbent assay (ELISA). The compositions of vaginal microbiomes were assessed by analysis of the V1-V3 regions of 16S rRNA genes, while cervical length was determined by transvaginal ultrasonography. The vaginal microbiomes could be clustered into five community state types (CSTs), four of which were dominated by a single Lactobacillus species. The dominance of Lactobacillus crispatus or Lactobacillus jensenii in the vaginal microbiome predicted the level of d-lactic acid present. Several of the biomarkers, especially TIMP-1, in combination with the subject’s age and race, were significantly associated with cervical length. Using piecewise structural equation modeling, we established a causal network that links CST to cervical length via biomarkers. We concluded that measuring levels of TIMP-1 and d-lactic acid in vaginal secretions might be a straightforward way to assess the risk for preterm birth due to a short cervix and microbiome composition. IMPORTANCE Premature birth and its complications are the largest contributors to infant death in the United States and globally. A short cervical length and the depletion of Lactobacillus species are known risk factors for preterm birth. However, in many resource-poor areas of the world, the technology to test for their occurrence is unavailable, and pregnant women with these risk factors are neither identified nor treated. In this study, we used path analysis to gain an unprecedented understanding of interactions between vaginal microbiome composition, the concentrations of various compounds in vaginal secretions, and cervical length. We identified low-cost point-of-care measures that might be used to identify pregnant women at risk for preterm birth. The use of these measures coupled with appropriate preventative or treatment strategies could reduce the incidence of preterm births in poor areas of the world that lack access to more sophisticated diagnostic methods.Steven S. WitkinAntonio F. MoronBenjamin J. RidenhourEvelyn MinisAlan HatanakaStephanno G. P. SarmentoMarcelo S. FrancaFrancisco H. C. CarvalhoTatiana K. HamamotoRosiane MattarEster SabinoIara M. LinharesMarilza V. C. RudgeLarry J. ForneyAmerican Society for Microbiologyarticlecervical lengthd-lactic acidpreterm birthTIMP-1vaginal microbiomeLactobacillusMicrobiologyQR1-502ENmBio, Vol 10, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	cervical length d-lactic acid preterm birth TIMP-1 vaginal microbiome Lactobacillus Microbiology QR1-502
spellingShingle	cervical length d-lactic acid preterm birth TIMP-1 vaginal microbiome Lactobacillus Microbiology QR1-502 Steven S. Witkin Antonio F. Moron Benjamin J. Ridenhour Evelyn Minis Alan Hatanaka Stephanno G. P. Sarmento Marcelo S. Franca Francisco H. C. Carvalho Tatiana K. Hamamoto Rosiane Mattar Ester Sabino Iara M. Linhares Marilza V. C. Rudge Larry J. Forney Vaginal Biomarkers That Predict Cervical Length and Dominant Bacteria in the Vaginal Microbiomes of Pregnant Women
description	ABSTRACT In many impoverished regions of the world, it may not be possible to assess two major risk factors for preterm birth: a short cervical length and the depletion of vaginal lactobacilli. We determined whether measuring specific compounds in vaginal fluid might be a simple, noninvasive, and cost-effective way to predict the bacteria that dominate the vaginal microbiome and indicate the presence of a shortened cervix (<25 mm). Vaginal fluid samples were prospectively collected from mid-trimester pregnant women, and the concentrations of d- and l-lactic acid, tissue inhibitor of matrix metalloproteinases TIMP-1 and TIMP-2, matrix metalloproteinases MMP-2 and MMP-8, the 70-kDa heat shock protein, a2 isoform of vacuolar ATPase, and sequestrome-1 were quantified by an enzyme-linked immunosorbent assay (ELISA). The compositions of vaginal microbiomes were assessed by analysis of the V1-V3 regions of 16S rRNA genes, while cervical length was determined by transvaginal ultrasonography. The vaginal microbiomes could be clustered into five community state types (CSTs), four of which were dominated by a single Lactobacillus species. The dominance of Lactobacillus crispatus or Lactobacillus jensenii in the vaginal microbiome predicted the level of d-lactic acid present. Several of the biomarkers, especially TIMP-1, in combination with the subject’s age and race, were significantly associated with cervical length. Using piecewise structural equation modeling, we established a causal network that links CST to cervical length via biomarkers. We concluded that measuring levels of TIMP-1 and d-lactic acid in vaginal secretions might be a straightforward way to assess the risk for preterm birth due to a short cervix and microbiome composition. IMPORTANCE Premature birth and its complications are the largest contributors to infant death in the United States and globally. A short cervical length and the depletion of Lactobacillus species are known risk factors for preterm birth. However, in many resource-poor areas of the world, the technology to test for their occurrence is unavailable, and pregnant women with these risk factors are neither identified nor treated. In this study, we used path analysis to gain an unprecedented understanding of interactions between vaginal microbiome composition, the concentrations of various compounds in vaginal secretions, and cervical length. We identified low-cost point-of-care measures that might be used to identify pregnant women at risk for preterm birth. The use of these measures coupled with appropriate preventative or treatment strategies could reduce the incidence of preterm births in poor areas of the world that lack access to more sophisticated diagnostic methods.
format	article
author	Steven S. Witkin Antonio F. Moron Benjamin J. Ridenhour Evelyn Minis Alan Hatanaka Stephanno G. P. Sarmento Marcelo S. Franca Francisco H. C. Carvalho Tatiana K. Hamamoto Rosiane Mattar Ester Sabino Iara M. Linhares Marilza V. C. Rudge Larry J. Forney
author_facet	Steven S. Witkin Antonio F. Moron Benjamin J. Ridenhour Evelyn Minis Alan Hatanaka Stephanno G. P. Sarmento Marcelo S. Franca Francisco H. C. Carvalho Tatiana K. Hamamoto Rosiane Mattar Ester Sabino Iara M. Linhares Marilza V. C. Rudge Larry J. Forney
author_sort	Steven S. Witkin
title	Vaginal Biomarkers That Predict Cervical Length and Dominant Bacteria in the Vaginal Microbiomes of Pregnant Women
title_short	Vaginal Biomarkers That Predict Cervical Length and Dominant Bacteria in the Vaginal Microbiomes of Pregnant Women
title_full	Vaginal Biomarkers That Predict Cervical Length and Dominant Bacteria in the Vaginal Microbiomes of Pregnant Women
title_fullStr	Vaginal Biomarkers That Predict Cervical Length and Dominant Bacteria in the Vaginal Microbiomes of Pregnant Women
title_full_unstemmed	Vaginal Biomarkers That Predict Cervical Length and Dominant Bacteria in the Vaginal Microbiomes of Pregnant Women
title_sort	vaginal biomarkers that predict cervical length and dominant bacteria in the vaginal microbiomes of pregnant women
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/05b6c89f3a3e4d8a80b9c75a9742053a
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Vaginal Biomarkers That Predict Cervical Length and Dominant Bacteria in the Vaginal Microbiomes of Pregnant Women

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