The vaginal immunoproteome for the prediction of spontaneous preterm birth: A retrospective longitudinal study

eLife, Год журнала: 2024, Номер 13

Опубликована: Июнь 24, 2024

Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Most cases preterm occur spontaneously result from labor with intact (spontaneous [sPTL]) or ruptured (preterm prelabor rupture membranes [PPROM]) membranes. The prediction spontaneous (sPTB) remains underpowered due to its syndromic nature dearth independent analyses vaginal host immune response. Thus, we conducted largest longitudinal investigation targeting mediators, referred herein as immunoproteome, in a population at high risk for sPTB. Vaginal swabs were collected across gestation pregnant women who ultimately underwent term birth, sPTL, PPROM. Cytokines, chemokines, growth factors, antimicrobial peptides samples quantified via specific sensitive immunoassays. Predictive models constructed mediator concentrations. Throughout uncomplicated gestation, immunoproteome harbors cytokine network homeostatic profile. Yet, skewed toward pro-inflammatory state experience sPTL Such an inflammatory profile includes increased monocyte chemoattractants, cytokines indicative macrophage T-cell activation, reduced proteins/peptides. has improved predictive value over maternal characteristics alone identifying early (<34 weeks) undergoes changes throughout deviations this shift are associated Furthermore, can be leveraged potential biomarker sPTB, subset sPTB extremely adverse outcomes. This research was by Perinatology Research Branch, Division Obstetrics Maternal-Fetal Medicine, Intramural Research, Eunice Kennedy Shriver National Institute Child Health Human Development, Institutes Health, U.S. Department Services (NICHD/NIH/DHHS) under contract HHSN275201300006C. ALT, KRT, NGL supported Wayne State University Perinatal Initiative Maternal, Health.

Язык: Английский

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Ureaplasma and Prevotella colonization with Lactobacillus abundance during pregnancy facilitates term birth

Scientific Reports, Год журнала: 2022, Номер 12(1)

Опубликована: Июнь 16, 2022

Abstract Ureaplasma and Prevotella infections are well-known bacteria associated with preterm birth. However, the development of metagenome sequencing techniques, it has been found that not all colonizations cause The purpose this study was to determine association between colonization induction birth even in presence Lactobacillus . In matched case–control study, a total 203 pregnant Korean women were selected their cervicovaginal fluid samples collected during mid-pregnancy. microbiome profiles analyzed using 16S rRNA gene amplification. Sequencing data processed QIIME1.9.1. Statistical analyses performed R software, analysis MicrobiomeAnalyst Calypso software. A positive correlation other genera highly related birth, but interestingly, there negative term same pattern observed Prevotella. abundance pregnancy facilitates although Balanced is important prevent

Язык: Английский

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A new approach to testing mediation of the microbiome at both the community and individual taxon levels

Bioinformatics, Год журнала: 2022, Номер 38(12), С. 3173 - 3180

Опубликована: Май 2, 2022

Understanding whether and which microbes played a mediating role between an exposure disease outcome are essential for researchers to develop clinical interventions treat the by modulating microbes. Existing methods mediation analysis of microbiome often limited global test community-level or selection without control false discovery rate (FDR). Further, while null hypothesis no at each microbe is composite that consists three types null, most existing as if they were all under same type leading excessive positive results.We propose new approach based on inverse regression regresses data taxon exposure-adjusted outcome. Then, P-values testing coefficients used both community individual levels. This fits nicely into our Linear Decomposition Model (LDM) framework, so method LDM-med, implemented in LDM enjoys features LDM, e.g. allowing arbitrary number taxa be tested simultaneously, supporting continuous, discrete, multivariate exposures outcomes (including survival outcomes), on. Using extensive simulations, we showed LDM-med always preserved FDR had adequate sensitivity; controlled I error compelling power over methods. The flexibility variety analyses illustrated application murine dataset, identified several plausible taxa.Our has been added R package available GitHub https://github.com/yijuanhu/LDM.Supplementary Bioinformatics online.

Язык: Английский

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Microbiota dynamics, metabolic and immune interactions in the cervicovaginal environment and their role in spontaneous preterm birth

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Дек. 22, 2023

Differences in the cervicovaginal microbiota are associated with spontaneous preterm birth (sPTB), a significant cause of infant morbidity and mortality. Although establishing direct causal link between sPTB remains challenging, recent advancements sequencing technologies have facilitated identification microbial markers potentially linked to sPTB. Despite variations findings, recurring observation suggests that is more diverse less stable vaginal across pregnancy trimesters. It hypothesized risk likely be modified via an intricate host-microbe interactions rather than due presence single taxon or broad community state. Nonetheless, lactobacilli dominance generally term outcomes contributes healthy environment through production lactic acid/maintenance low pH excludes other pathogenic microorganisms. Additionally, innate immunity host metabolic microbiota, such as bacteriocins use proteolytic enzymes, exerts profound influence on populations, activities, immune responses. These interplays collectively impact outcomes. This review aims summarize complexity dynamics, associations bacterial vaginosis There also consideration how probiotics may mitigate vaginosis.

Язык: Английский

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Microbiota of the Pregnant Mouse: Characterization of the Bacterial Communities in the Oral Cavity, Lung, Intestine, and Vagina through Culture and DNA Sequencing

Microbiology Spectrum, Год журнала: 2022, Номер 10(4)

Опубликована: Авг. 2, 2022

Mice are frequently used as animal models for mechanistic studies of infection and obstetrical disease, yet characterization the murine microbiota during pregnancy is lacking. The objective this study was to characterize microbiotas distinct body sites pregnant mouse-vagina, oral cavity, intestine, lung-that harbor microorganisms that could potentially invade amniotic thus leading adverse outcomes. these were characterized through anoxic, hypoxic, oxic culture well 16S rRNA gene sequencing. With exception vagina, cultured each site varied by atmosphere, with greatest diversity in appearing under anoxic conditions. Only cultures vagina comprehensively representative observed direct DNA sequencing samples, primarily due predominance two Rodentibacter strains. Identified pneumotropicus heylii, isolates exhibited patterns similar those Lactobacillus crispatus iners human vagina. Whole-genome strains revealed shared genomic features, including ability degrade glycogen, an abundant polysaccharide In summary, we report site-specific mouse potential ecological parallels humans. Importantly, our findings indicate vaginal mice can be readily cultured, suggesting mock tractably generated maintained experimental manipulation future host vaginal-microbiome interactions. IMPORTANCE widely utilized complications; however, has been neglected. Microorganisms from lung have found intra-amniotic space, where their presence threatens progression gestation. Here, established appropriateness capturing at site. high relative abundance humans, parallels. hypoxic conditions, demonstrating microbial communities test between evaluate relevance structure outcomes, especially preterm birth.

Язык: Английский

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