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Microbiology Spectrum Jun 2024The microbial ecosystem of women undergoes enormous changes during pregnancy and the perinatal period. Little is known about the extent of changes in the maternal...
UNLABELLED
The microbial ecosystem of women undergoes enormous changes during pregnancy and the perinatal period. Little is known about the extent of changes in the maternal microbiome beyond the vaginal cavity and its recovery after birth. In this study, we followed pregnant women [maternal prepartum (mpre), = 30] into the postpartum period [1 month postpartum, maternal postpartum (mpost), = 30]. We profiled their oral, urinary, and vaginal microbiome; archaeome; mycobiome; and urinary metabolome and compared them with those of nonpregnant (np) women ( = 29). Overall, pregnancy status (np, mpre, and mpost) had a smaller effect on the microbiomes than body site, but massive transitions were observed for the oral and urogenital (vaginal and urinary) microbiomes. While the oral microbiome fluctuates during pregnancy but stabilizes rapidly within the first month postpartum, the urogenital microbiome is characterized by a major remodeling caused by a massive loss of and thus a shift from Vaginal Community State Type (CST) I (40% of women) to CST IV (85% of women). The urinary metabolome rapidly reached an np-like composition after delivery, apart from lactose and oxaloacetic acid, which were elevated during active lactation. Fungal and archaeal profiles were indicative of pregnancy status. signatures were found mainly in np women, and showed an opposite behavior in the oral cavity (increased) and vagina (decreased) during pregnancy. Our findings suggest that the massive remodeling of the maternal microbiome and metabolome needs more attention and that potential interventions could be envisioned to optimize recovery and avoid long-term effects on maternal health and subsequent pregnancies.
IMPORTANCE
The perinatal microbiome is of specific interest for the health of the mother and infant. We therefore investigate the dynamics of the female microbiome from nonpregnant over prepartum to the postpartum period in urine and the oral and vaginal cavities. A specific focus of this study is put not only on the bacterial part of the microbiome but also on the underinvestigated contribution of fungi and archaea. To our knowledge, we present the first study highlighting those aspects. Our findings suggest that the massive remodeling of the maternal microbiome and metabolome needs more attention and that potential interventions could be envisioned to optimize recovery and avoid long-term effects on maternal health and subsequent pregnancies.
PubMed: 38917430
DOI: 10.1128/spectrum.00147-24 -
Journal of Obstetrics and Gynaecology :... Dec 2024The aim is to investigate the risk of short-term maternal morbidity caused by the selective clinical use of episiotomy (rate < 0.02), and to compare the risk of severe...
BACKGROUND
The aim is to investigate the risk of short-term maternal morbidity caused by the selective clinical use of episiotomy (rate < 0.02), and to compare the risk of severe perineal tears with the statewide risk.
METHODS
In this retrospective cohort study, we investigated the effect of selective episiotomy on the risk of severe perineal tears and blood loss in singleton term deliveries, using propensity scores with inverse probability weighting.
RESULTS
This study included 10992 women who delivered vaginally between 2008-2018. Episiotomy was performed in 171 patients (1.55%), three of whom (1.75%) experienced severe perineal tears compared to 156 (1.44%) in the control cohort. The adjusted odds ratio of severe perineal tears was 2.06 (95% confidence interval [CI]: 0.51, 8.19 with 0.3 value). Multivariate linear regression showed that episiotomy increased blood loss by 96.3 ml (95% CI: 6.4, 186.2 with 0.03 value). Episiotomy was performed in 23% (95% CI: 0.228, 0.23) of vaginal deliveries in the state of Hessen, with a risk of severe perineal tears of 0.0143 (95% CI: 0.0139, 0.0147) compared to 0.0145 (95% CI: 0.0123, 0.0168) in our entire cohort.
CONCLUSIONS
Selective use of episiotomy does not increase the risk of higher-grade perineal tears. However, it may be associated with maternal morbidity in terms of increased blood loss.
Topics: Humans; Female; Episiotomy; Retrospective Studies; Pregnancy; Adult; Perineum; Obstetric Labor Complications; Delivery, Obstetric; Risk Factors; Lacerations; Propensity Score; Postpartum Hemorrhage; Young Adult
PubMed: 38917046
DOI: 10.1080/01443615.2024.2369664 -
BioRxiv : the Preprint Server For... Jun 2024Group B (GBS) asymptomatically colonizes the vagina but can opportunistically ascend to the uterus and be transmitted vertically during pregnancy, resulting in neonatal...
UNLABELLED
Group B (GBS) asymptomatically colonizes the vagina but can opportunistically ascend to the uterus and be transmitted vertically during pregnancy, resulting in neonatal pneumonia, bacteremia and meningitis. GBS is a leading etiologic agent of neonatal infection and understanding the mechanisms by which GBS persists within the polymicrobial female genital mucosa has potential to mitigate subsequent transmission and disease. Type VIIb secretion systems (T7SSb) are encoded by Firmicutes and often mediate interbacterial competition using LXG toxins that contain conserved N-termini important for secretion and variable C-terminal toxin domains that confer diverse biochemical activities. Our recent work characterized a role for the GBS T7SSb in vaginal colonization and ascending infection but the mechanisms by which the T7SSb promotes GBS persistence in this polymicrobial niche remain unknown. Herein, we investigate the GBS T7SS in interbacterial competition and GBS niche establishment in the female genital tract. We demonstrate GBS T7SS-dependent inhibition of mucosal pathobiont both using predator-prey assays and in the murine genital tract and found that a GBS LXG protein encoded within the T7SS locus (herein named group B streptococcal L XG T oxin A ) that contributes to these phenotypes. We identify BltA as a T7SS substrate that is toxic to and upon induction of expression along with associated chaperones. Finally, we show that BltA and its chaperones contribute to GBS vaginal colonization. Altogether, these data reveal a role for a novel T7b-secreted toxin in GBS mucosal persistence and competition.
IMPORTANCE
Competition between neighboring, non-kin bacteria is essential for microbial niche establishment in mucosal environments. Gram-positive bacteria encoding T7SSb have been shown to engage in competition through export of LXG-motif containing toxins, but these have not been characterized in group B (GBS), an opportunistic colonizer of the polymicrobial female genital tract. Here, we show a role for GBS T7SS in competition with mucosal pathobiont , both and . We further find that a GBS LXG protein contributing to this antagonism is exported by the T7SS and is intracellularly toxic to other bacteria; therefore, we have named this protein group B streptococcal L XG T oxin A (BltA). Finally, we show that BltA and its associated chaperones promote persistence within female genital tract tissues These data reveal previously unrecognized mechanisms by which GBS may compete with other mucosal opportunistic pathogens to persist within the female genital tract.
PubMed: 38915665
DOI: 10.1101/2024.06.10.598350 -
Archives of Public Health = Archives... Jun 2024Human Papillomavirus (HPV) is implicated in the pathogenesis of cancer in the cervix, vagina, throat and anogenital region. Although HPV vaccination rates in the...
Impact of the COVID-19 pandemic on HPV vaccine uptake in a predominantly Hispanic Border Community: A retrospective cross-sectional analysis of the "Tiempo de Vacunarte Program".
BACKGROUND
Human Papillomavirus (HPV) is implicated in the pathogenesis of cancer in the cervix, vagina, throat and anogenital region. Although HPV vaccination rates in the Hispanic community have increased owing to public health efforts, the COVID-19 pandemic has brought unique public health challenges and contributed to health inequity in this population.
METHODS
To evaluate the impact of the COVID-19 pandemic on HPV vaccine uptake in a program designed to improve HPV vaccination rate in a predominantly Hispanic community in the border region of Texas (Tiempo de Vacunarte [time to get vaccinated]), we performed a retrospective cross-sectional analysis to evaluate the uptake of the first dose of HPV vaccine series among eligible adolescents and adults before (2016-2019), during (2020-2021), and after the COVID-19 pandemic (2022-2023).
RESULTS
We observed a decrease in HPV vaccine uptake during the pandemic (69.59% vs. 89.92%) and post-pandemic (76% vs. 89.92%) compared to the pre-pandemic period. After adjusting for confounding factors, the reduction in the odds ratio was more pronounced in the pandemic (OR = 0.091, p < 0.001) and post-pandemic (OR = 0.109, p < 0.001) periods.
CONCLUSION
Our findings suggest that the COVID-19 pandemic significantly impacted the uptake of the HPV vaccine in a comprehensive intervention program to increase HPV vaccination in a border community.
PubMed: 38915042
DOI: 10.1186/s13690-024-01318-0 -
ELife Jun 2024Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Most cases of preterm birth occur spontaneously and result from preterm labor with...
BACKGROUND
Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Most cases of preterm birth occur spontaneously and result from preterm labor with intact (spontaneous preterm labor [sPTL]) or ruptured (preterm prelabor rupture of membranes [PPROM]) membranes. The prediction of spontaneous preterm birth (sPTB) remains underpowered due to its syndromic nature and the dearth of independent analyses of the vaginal host immune response. Thus, we conducted the largest longitudinal investigation targeting vaginal immune mediators, referred to herein as the immunoproteome, in a population at high risk for sPTB.
METHODS
Vaginal swabs were collected across gestation from pregnant women who ultimately underwent term birth, sPTL, or PPROM. Cytokines, chemokines, growth factors, and antimicrobial peptides in the samples were quantified via specific and sensitive immunoassays. Predictive models were constructed from immune mediator concentrations.
RESULTS
Throughout uncomplicated gestation, the vaginal immunoproteome harbors a cytokine network with a homeostatic profile. Yet, the vaginal immunoproteome is skewed toward a pro-inflammatory state in pregnant women who ultimately experience sPTL and PPROM. Such an inflammatory profile includes increased monocyte chemoattractants, cytokines indicative of macrophage and T-cell activation, and reduced antimicrobial proteins/peptides. The vaginal immunoproteome has improved predictive value over maternal characteristics alone for identifying women at risk for early (<34 weeks) sPTB.
CONCLUSIONS
The vaginal immunoproteome undergoes homeostatic changes throughout gestation and deviations from this shift are associated with sPTB. Furthermore, the vaginal immunoproteome can be leveraged as a potential biomarker for early sPTB, a subset of sPTB associated with extremely adverse neonatal outcomes.
FUNDING
This research was conducted by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS) under contract HHSN275201300006C. ALT, KRT, and NGL were supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health.
Topics: Humans; Female; Longitudinal Studies; Pregnancy; Vagina; Premature Birth; Adult; Retrospective Studies; Proteome; Cytokines; Fetal Membranes, Premature Rupture; Young Adult; Immunoproteins
PubMed: 38913421
DOI: 10.7554/eLife.90943 -
Frontiers in Cellular and Infection... 2024We assessed the anti-chlamydial activity of fresh vaginal secretions, deciphering the microbial and metabolic components able to counteract viability.
INTRODUCTION
We assessed the anti-chlamydial activity of fresh vaginal secretions, deciphering the microbial and metabolic components able to counteract viability.
METHODS
Forty vaginal samples were collected from a group of reproductive-aged women and their anti-chlamydial activity was evaluated by inhibition experiments. Each sample underwent 16S rRNA metabarcoding sequencing to determine the bacterial composition, as well as H-NMR spectroscopy to detect and quantify the presence of vaginal metabolites.
RESULTS
Samples characterized by a high anti-chlamydial activity were enriched in , especially and , while not-active samples exhibited a significant reduction of lactobacilli, along with higher relative abundances of and . showed an opposite behavior compared to , being more prevalent in not-active vaginal samples. Higher concentrations of several amino acids (i.e., isoleucine, leucine, and aspartate; positively correlated to the abundance of and ) lactate, and 4-aminobutyrate were the most significant metabolic fingerprints of highly active samples. Acetate and formate concentrations, on the other hand, were related to the abundances of a group of anaerobic opportunistic bacteria (including and ). Finally, glucose, correlated to and genera, emerged as a key molecule of the vaginal environment: indeed, the anti-chlamydial effect of vaginal fluids decreased as glucose concentrations increased.
DISCUSSION
These findings could pave the way for novel strategies in the prevention and treatment of chlamydial urogenital infections, such as lactobacilli probiotic formulations or lactobacilli-derived postbiotics.
Topics: Female; Humans; Vagina; RNA, Ribosomal, 16S; Lactobacillus; Chlamydia trachomatis; Adult; Streptococcus; Young Adult; Lactobacillus crispatus; Chlamydia Infections
PubMed: 38912205
DOI: 10.3389/fcimb.2024.1403782 -
Scientific Reports Jun 2024Vaginitis, a prevalent gynecological condition in women, is mainly caused by an imbalance in the vaginal micro-ecology. The two most common types of vaginitis are...
Vaginitis, a prevalent gynecological condition in women, is mainly caused by an imbalance in the vaginal micro-ecology. The two most common types of vaginitis are vaginal bacteriosis and vulvovaginal candidiasis, triggered by the virulent Gardnerella vaginalis and Candida albicans, respectively. In this study, a strain capable of inhibiting G. vaginalis and C. albicans was screened from vaginal secretions and identified as Lactobacillus gasseri based on 16S rRNA sequences. The strain, named L. gasseri VHProbi E09, could inhibit the growth of G. vaginalis and C. albicans under co-culture conditions by 99.07% ± 0.26% and 99.95% ± 0.01%, respectively. In addition, it could significantly inhibit the adhesion of these pathogens to vaginal epithelial cells. The strain further showed the ability to inhibit the enteropathogenic bacteria Escherichia coli and Salmonella enteritidis, to tolerate artificial gastric and intestinal fluids and to adhere to intestinal Caco-2 cells. These results suggest that L. gasseri VHProbi E09 holds promise for clinical trials and animal studies whether administered orally or directly into the vagina. Whole-genome analysis also revealed a genome consisting of 1752 genes for L. gasseri VHProbi E09, with subsequent analyses identifying seven genes related to adhesion and three genes related to bacteriocins. These adhesion- and bacteriocin-related genes provide a theoretical basis for understanding the mechanism of bacterial inhibition of the strain. The research conducted in this study suggests that L. gasseri VHProbi E09 may be considered as a potential probiotic, and further research can delve deeper into its efficacy as an agent which can restore a healthy vaginal ecosystem.
Topics: Female; Probiotics; Humans; Lactobacillus gasseri; Caco-2 Cells; Gardnerella vaginalis; Candida albicans; Vagina; Bacterial Adhesion; Vaginitis; RNA, Ribosomal, 16S
PubMed: 38910172
DOI: 10.1038/s41598-024-65550-y -
Journal of Gynecology Obstetrics and... Jun 2024Urinary incontinence affects 25-45% of women with the gold standard surgical approach being placement of mid-urethral synthetic slings; tension-free vaginal tape (TVT)...
Urinary incontinence affects 25-45% of women with the gold standard surgical approach being placement of mid-urethral synthetic slings; tension-free vaginal tape (TVT) and trans-obturator tape (TOT). Due to the controversies regarding vaginal mesh the last decade, an increasing demand has evolved for incontinence treatment without vaginal synthetic mesh. The short term results of autologous rectus fascia sling for TOT surgery have shown similar success rates compared to those after the use of synthetic mesh, but the harvesting of the mesh is less minimally invasive and is associated with longer surgical time. vNOTES is a combination of a vaginal entrance to the abdomen and endoscopy via the vagina. The aim with the video is to show a new surgical technique with a fully vaginal, scarless vNOTES approach for harvesting the posterior rectus fascia for TVT and TOT procedures.
PubMed: 38909957
DOI: 10.1016/j.jogoh.2024.102816 -
Mucosal Immunology Jun 2024Regulatory T cells (Treg) are well-known to mediate peripheral tolerance at homeostasis, and there is growing appreciation for their role in modulating infectious...
Regulatory T cells (Treg) are well-known to mediate peripheral tolerance at homeostasis, and there is growing appreciation for their role in modulating infectious disease immunity. Following acute and chronic infections, Tregs can restrict pathogen-specific T cell responses to limit immunopathology. However, it is unclear if Tregs mediate control of pathology and immunity in distal tissue sites during localized infections. We investigated a role for Tregs in immunity and disease in various tissue compartments in the context of "mild" vaginal Zika virus (ZIKV) infection. We found that Tregs are critical to generate robust virus-specific CD8 T cell responses in the initial infection site. Further, Tregs limit inflammatory cytokines and immunopathology during localized infection; a dysregulated immune response in Treg-depleted mice leads to increased T cell infiltrates and immunopathology in both the vagina and the central nervous system (CNS). Importantly, these CNS infiltrates are not present at the same magnitude during infection of Treg sufficient mice, in which there is not CNS immunopathology. Our data suggest that Tregs are necessary to generate a robust virus-specific response at the mucosal site of infection, while Treg-mediated restriction of bystander inflammation limits immunopathology both at the site of infection as well as distal tissue sites.
PubMed: 38908483
DOI: 10.1016/j.mucimm.2024.06.007 -
Microbiome Jun 2024Bacterial vaginosis (BV) increases HIV acquisition risk, potentially by eliciting genital inflammation. After BV treatment, the vaginal administration of LACTIN-V, a...
BACKGROUND
Bacterial vaginosis (BV) increases HIV acquisition risk, potentially by eliciting genital inflammation. After BV treatment, the vaginal administration of LACTIN-V, a live biotherapeutic containing the Lactobacillus crispatus strain CTV-05, reduced BV recurrence and vaginal inflammation; however, 3 months after product cessation, CTV-05 colonization was only sustained in 48% of participants.
RESULTS
This nested sub-study in 32 participants receiving LACTIN-V finds that 72% (23/32) demonstrate clinically relevant colonization (CTV-05 absolute abundance > 10 CFU/mL) during at least one visit while 28% (9/32) of women demonstrate colonization resistance, even during product administration. Immediately prior to LACTIN-V administration, the colonization-resistant group exhibited elevated vaginal microbiota diversity. During LACTIN-V administration, colonization resistance was associated with elevated vaginal markers of epithelial disruption and reduced chemokines, possibly due to elevated absolute abundance of BV-associated species and reduced L. crispatus. Colonization permissive women were stratified into sustained and transient colonization groups (31% and 41% of participants, respectively) based on CTV-05 colonization after cessation of product administration. These groups also exhibited distinct genital immune profiles during LACTIN-V administration.
CONCLUSIONS
The genital immune impact of LACTIN-V may be contingent on the CTV-05 colonization phenotype, which is in turn partially dependent on the success of BV clearance prior to LACTIN-V administration.
Topics: Humans; Female; Vaginosis, Bacterial; Vagina; Lactobacillus crispatus; Adult; Probiotics; Administration, Intravaginal; Microbiota; Young Adult; Phenotype
PubMed: 38907268
DOI: 10.1186/s40168-024-01828-7