Project description:Clinical treatment protocols for infertility with in vitro fertilization-embryo transfer (IVF-ET) provide a unique opportunity to assess the human vaginal microbiome in defined hormonal milieu. Herein, we have investigated the association of circulating ovarian-derived estradiol (E2) and progesterone (P4) concentrations to the vaginal microbiome. Thirty IVF-ET patients were enrolled in this study, after informed consent. Blood was drawn at four time points during the IVF-ET procedure. In addition, if a pregnancy resulted, blood was drawn at 4-to-6 weeks of gestation. The serum concentrations of E2 and P4 were measured. Vaginal swabs were obtained in different hormonal milieu. Two independent genome-based technologies (and the second assayed in two different ways) were employed to identify the vaginal microbes. The vaginal microbiome underwent a transition with a decrease in E2 (and/or a decrease in P4). Novel bacteria were found in the vagina of 33% of the women undergoing IVF-ET. Our approach has enabled the discovery of novel, previously unidentified bacterial species in the human vagina in different hormonal milieu. While the relationship of hormone concentration and vaginal microbes was found to be complex, the data support a shift in the microbiome of the human vagina during IVF-ET therapy using standard protocols. The data also set the foundation for further studies examining correlations between IVF-ET outcome and the vaginal microbiome within a larger study population.
Project description:Characterization of the microbiome in vaginal and stool samples self-sampled from endometrial cancer survivors enrolled in the Carolina Endometrial Cancer Study.
Project description:Griffithsin (GRFT) is an anti-viral lectin with potent anti-HIV activity. GRFT’s preclinical safety, lack of systemic absorption after topical administration, and lack of cross-resistance with existing products prompted its development for topical HIV pre-exposure prophylaxis. We evaluated safety, pharmacokinetics and pharmacodynamics of PC-6500 (0.1% GRFT in a carrageenan (CG) gel) in healthy, HIV-negative, non-pregnant women following once daily vaginal gel administration for 14 days. No significant adverse events, histopathological changes in cervico-vaginal mucosa, or anti-drug (GRFT) antibodies were detected. No cervicovaginal proinflammatory responses and no changes in the ectocervical transcriptome were evident. Vaginal microbiome remained largely unchanged. Reduced abundance of vaginosis-associated bacteria and decreased levels of proinflammatory chemokines (CXCL8 and CCL20) were observed. GRFT was not detected in plasma. GRFT and GRFT/CG in CVLs dose-dependently inhibited HIV and HPV, respectively, in vitro. The data suggest GRFT/CG is a promising on-demand multipurpose prevention product that warrants further investigation.
Project description:The goal of this study was to identify amylases that might be present in the vaginal fluid from four individual donors coming either from the microbiome or expressed by the human donors in these fluids. We collected cervicovaginal mucus from 4 donors, characterized the species composition of vaginal communities by genome sequencing. Samples were digested with trypsin, then analyzed by LC-MS/MS. Data was searched with MaxQuant and downstream data analysis was performed using RomicsProcessor.
Project description:To comprehensively describe both host gene expression and microbiome composition in a single sample, parallel experimental and computational workflows -mRNA sequencing and either 16S or metagenomics- have been traditionally applied. Here, following in vitro validation of the reliability of Poly(A)-enriched mRNA sequencing in reconstructing the microbiota composition on a defined microbial mock community, we process a cohort of 30 vulvar mRNA-seq samples to fully analyze not only the transcriptome of the vulvar cells, but also the composition of microbial communities and their parallel changes. This three-level analysis on the very same specimens further enables a gene-level exploration of the reciprocal molecular crosstalk between host and microbes. The vulvar milieu represents an area of emerging research for its role in health and disease. Being at the anatomical intersection between the vaginal milieu and the perineal area, the vulvar microbiome displays an intermediate signature, with contamination from both ecosystems. Using this unified framework, we reveal marked heterogeneity and high inter-individual variability in the vulvar microbiota of healthy individuals, identifying community state types that mirror those described in the vaginal ecosystem. Importantly, we show that distinct microbial configurations are associated with specific host transcriptional programs: Lactobacillus crispatus dominated communities correlate with epithelial differentiation and barrier integrity, whereas communities enriched in taxa associated with dysbiosis exhibit transcriptional signatures linked to inflammation. Beyond providing new biological insights into an understudied anatomical niche, our study introduces a broadly applicable strategy with substantial impact for the field. With tens of thousands of human RNA-seq datasets already available in public repositories, our approach enables retrospective extraction of microbiome information and host-microbe interaction signals from existing transcriptomic data, without the need for additional sequencing or specialized microbiome protocols. This unlocks a powerful and cost-effective opportunity to revisit archived RNA-seq studies across tissues, diseases, and low-biomass environments, revealing previously inaccessible layers of host-microbiome crosstalk and maximizing the scientific value of data that already exist.
Project description:<p>The human vaginal microbiome, particularly its symbiosis with lactobacilli, plays a key role in maintaining women’s health. While lactic acid-mediated pathogen exclusion is well known, broader metabolic functions of vaginal lactobacilli remain underexplored. In this study, we analyzed the vaginal microbiome and metabolome of 258 healthy women from the Isala program. Using targeted HILIC-QTOF MS, we detected a high prevalence of most B-vitamins, their precursors, and vitamin A in the vaginal microenvironment. Riboflavin (B2) and biotin (B7) showed strong associations with Lactobacillus crispatus and Limosilactobacillus. Comparative genomics, phenotypic assays, and in vivo metatranscriptomic data (VIRGO2) collectively confirmed riboflavin biosynthesis by these taxa. Using a riboflavin overproducing Lim. reuteri as a functional probe, we show that microbially derived riboflavin and its intermediates are transported across the vaginal epithelium and modulate host redox balance, cytokine production, and activation of mucosal-associated invariant T (MAIT) cells via MR1 receptor induction, revealing a potential immunometabolic interface between host and microbiota.</p>