Epigenetics and the vaginal microbiome: influence of the microbiota on the histone deacetylase level in vaginal epithelial cells from pregnant women

Nasioudis, Dimitrios; Leizer, Julie; Minis, Evelyn; Boester, Allison; Forney, Larry J.

doi:10.23736/s0026-4784.18.04322-8

Cited by 9 publications

(7 citation statements)

References 16 publications

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“…The characteristics of each study that reported ( n = 13) ( Fettweis et al., 2014 ; Ghartey et al., 2014 ; Romero et al., 2014a ; Romero et al., 2014b ; Bisanz et al., 2015 ; MacIntyre et al., 2015 ; Kindinger et al., 2017 ; Brown et al., 2018 ; Hočevar et al., 2019 ; Purkayastha et al., 2019 ; Romero et al., 2019 ; Tabatabaei et al., 2019 ; Al-Memar et al., 2020 ) or did not report GBS ( n = 32) ( Dominguez-Bello et al., 2010 ; Hernández-Rodríguez et al., 2011 ; Aagaard et al., 2012 ; Frank et al., 2012 ; Hyman et al., 2012 ; Hyman et al., 2014 ; Walther-António et al., 2014 ; Baldwin et al., 2015 ; DiGiulio et al., 2015 ; Huang et al., 2015 ; Brumbaugh et al., 2016 ; Jayaprakash et al., 2016 ; Lauder et al., 2016 ; Nelson et al., 2016 ; Subramaniam et al., 2016 ; Callahan et al., 2017 ; Freitas et al., 2017 ; Nasioudis et al., 2017b ; Nasioudis et al., 2017a ; Roesch et al., 2017 ; Stout et al., 2017 ; Goltsman et al., 2018 ; Leizer et al., 2018 ; Matsumoto et al., 2018 ; Wylie et al., 2018 ; Chen et al., 2019 ; Dobbler et al., 2019 ; He et al., 2019 ; Jefferson et al., 2019 ; Liu et al., 2019 ; Price et al., 2019 ; Witkin et al., 2019 ) are described in Tables S1 and S2 respectively.…”

Section: Resultsmentioning

confidence: 99%

Group B Streptococcus and the vaginal microbiome among pregnant women: a systematic review

Lim

Rajagopal

Jeong

et al. 2021

PeerJ

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Background Vaginal microbiome studies frequently report diversity metrics and communities of microbiomes associated with reproductive health outcomes. Reports of Streptococcus agalactiae (also known as Group B Streptococcus or GBS), the leading cause of neonatal infectious morbidity and mortality, are notably lacking from the studies of the vaginal microbiome, despite being a known contributor to preterm birth and other complications. Therefore, the purpose of this systematic review was to explore the frequency of GBS reporting in vaginal microbiome literature pertaining to pregnancy and to examine methodological bias that contributes to differences in species and genus-level microbiome reporting. Lack of identification of GBS via sequencing-based approaches due to methodologic or reporting bias may result incomplete understanding of bacterial composition during pregnancy and subsequent birth outcomes. Methodology A systematic review was conducted following the PRISMA guideline. Three databases (PubMed, CINAHL, and Web of Science) were used to identify papers for review based on the search terms “vaginal microbiome”, “pregnancy”, and “16S rRNA sequencing”. Articles were evaluated for methods of DNA extraction and sequencing, 16S region, taxonomy classification database, number of participants or vaginal specimens, and pregnancy trimester. Results Forty-five research articles reported employing a metagenomic approach or 16S approach for vaginal microbiome analysis during pregnancy that explicitly reported taxonomic composition and were included in this review. Less than 30% of articles reported the presence of GBS (N = 13). No significant differences in methodology were identified between articles that reported versus did not report GBS. However, there was large variability across research methods used for vaginal microbiome analysis and species-level bacterial community reporting. Conclusion Considerable differences in study design and data formatting methods may contribute to underrepresentation of GBS, and other known pathogens, in existing vaginal microbiome literature. Previous studies have identified considerable variation in methodology across vaginal microbiome studies. This study adds to this body of work because in addition to laboratory or statistical methods, how results and data are shared (e.g., only analyzing genus level data or 20 most abundant microbes), may hinder reproducibility and limit our understanding of the influence of less abundant microbes. Sharing detailed methods, analysis code, and raw data may improve reproducibility and ability to more accurately compare microbial communities across studies.

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Section: Resultsmentioning

confidence: 99%

Group B Streptococcus and the vaginal microbiome among pregnant women: a systematic review

Lim

Rajagopal

Jeong

et al. 2021

PeerJ

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“…A reduced MMP-8 level as a result of L. crispatus-mediated release of D-lactic acid would minimize this consequence. A recent study has also demonstrated that the vaginal concentration of MMP-8 in pregnant women is positively associated with the level of histone deacetylase (HDAC) (17) . HDAC is an enzyme that regulates gene transcription by modulating the acetylation of histones in distinct chromosome regions (18) .…”

Section: Discussionmentioning

confidence: 98%

“…HDAC is an enzyme that regulates gene transcription by modulating the acetylation of histones in distinct chromosome regions (18) . There is a negative association between D-lactic acid and HDAC levels in the vagina during pregnancy (17) . Thus, by modulating the transcription of specific genes, D-lactic acid may enhance the ability of cells in the lower genital tract to successfully respond to exogenous or endogenous insults and maintain normal function.…”

Section: Discussionmentioning

confidence: 99%

Lactobacilluscrispatus dominance in the vaginalmicrobiome reduces the occurrence of spontaneouspreterm birth in women with a short cervical length

Moron

Linhares

Hatanaka

et al. 2022

J Bras Doenças Sex Transm

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Introduction: The majority of pregnant women with a short cervix will deliver at term and, thus, may unnecessarily receive advanced monitoring and treatment. It is still necessary to define more accurately which sub-population of women with a short cervix is at elevated risk for early delivery. Objective: To determine if vaginal microbiome composition influenced the rate of spontaneous preterm birth in women with a short cervical length. Methods: In an exploratory, observational prospective study, vaginal secretions were obtained from 591 women at 21–24 week gestation. Vaginal microbiome composition was determined by analyzing the V1–V3 region of the bacterial 16S ribosomal RNA gene. Results: Lactobacillus crispatus was numerically dominant in the vagina in 41.7% of subjects, followed by L. iners in 32% and Gardnerella vaginalis in 12%. In women whose cervix was ≤25mm, the sensitivity to predict an spontaneous preterm birth was 11.8%. However, when L. crispatus was not the dominant vaginal bacterium, this sensitivity increased to 81.8%. Similarly, in women with a cervical length ≤30mm, the sensitivity to predict an spontaneous preterm birth increased from 21.7 to 78.3% when L. crispatus was not the dominant vaginal bacterium.In women with a prior spontaneous preterm birth and a cervix ≤25 or ≤30mm, L. crispatus dominance was also associated with a reduced rate of spontaneous preterm birth in the current pregnancy (p<0.001). Conclusion: In pregnant women with a cervix ≤25mm or ≤30mm, the risk for an spontaneous preterm birth is increased if L. crispatus is not dominant in the vagina.

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“…no. IT4738; G-Biosciences) in the culture media according to the manufacturer's instructions and as described previously (31,32).…”

Section: Methodsmentioning

confidence: 99%

Effects of histone H4 hyperacetylation on inhibiting MMP2 and MMP9 in human amniotic epithelial cells and in premature rupture of fetal membranes

Song¹,

Yang²,

Hu³

et al. 2021

Exp Ther Med

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Histone modification is closely associated with several diseases. The aim of the current study was to investigate the associations among histone acetylation, matrix metalloproteinases (MMPs) and premature rupture of membranes (PROM) during pregnancy. A total of 180 puerperants were divided into three groups: i) Preterm-PROM (PPROM), ii) term-PROM (TPROM) and iii) full-term labor (FTL). Enzyme-linked immunosorbent assay (ELISA) kits and western blotting were used to determine the protein concentrations of MMP2, MMP9, histone deacetylase (HDAC)1, HDAC2 and HDAC6, and the protein levels of histone H4 lysine (H4K)5 and H4K8 acetylation, respectively, in three types of fetal membranes. Additionally, human amniotic epithelial cells were used to determine the effects of the HDAC inhibitors droxinostat and chidamide on cell viability, histone acetylation and the levels of MMP2, MMP9, HDAC1, HDAC2 and HDAC6 in vitro, using the Cell Counting Kit-8 assay, western blotting and ELISA, respectively. Furthermore, the effects of droxinostat and chidamide on the invasion and migration abilities of human amniotic epithelial cells were investigated using transwell assays. In fetal membranes, the activities of MMP2 and MMP9 increased in PPROM, but decreased in TPROM. Further, the expression of HDAC1 was decreased and histone hyperacetylation was increased in both PPROM and TRPOM. In vitro experiments revealed that 5 µM droxinostat and 0.5 µM chidamide selectively decreased the level of HDAC and induced acetylation of H4K5 and H4K8. Additionally, the aforementioned HDAC inhibitors reduced human amniotic epithelial cell viability, invasion and migration, and decreased the expression levels of MMP2 and MMP9. The current study revealed a high expression level of MMP2 and MMP9 in PPROM compared with TPROM and FL tissue, which was in accordance with previously published studies. Furthermore, the in vitro tests performed in the current study revealed the effect of histone H4 hyperacetylation on inhibiting MMP2 and MMP9 levels in vitro was similar to that observed in TPROM. The results obtained in the current study may be used as a theoretical guide for clinical treatment of premature rupture of membranes.

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Epigenetics and the vaginal microbiome: influence of the microbiota on the histone deacetylase level in vaginal epithelial cells from pregnant women

Cited by 9 publications

References 16 publications

Group B Streptococcus and the vaginal microbiome among pregnant women: a systematic review

Group B Streptococcus and the vaginal microbiome among pregnant women: a systematic review

Lactobacilluscrispatus dominance in the vaginalmicrobiome reduces the occurrence of spontaneouspreterm birth in women with a short cervical length

Effects of histone H4 hyperacetylation on inhibiting MMP2 and MMP9 in human amniotic epithelial cells and in premature rupture of fetal membranes

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