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Comparing probiotic potential of vaginal Lactobacillus isolates

ABSTRACT: Exploring the potential of vaginal Lactobacillus isolates from South African women for enhancing treatment for bacterial vaginosis

PROVIDER: PRJEB37955 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR4057072_1.fastq.gz	Fastqsanger.gz
	ERR4057072_2.fastq.gz	Fastqsanger.gz
	ERR4057073_1.fastq.gz	Fastqsanger.gz
	ERR4057073_2.fastq.gz	Fastqsanger.gz
	ERR4057064_1.fastq.gz	Fastqsanger.gz

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Vaginal epithelial dysfunction is mediated by the microbiome, metabolome, and mTOR signaling - Participant Group 1

Project description:Bacterial vaginosis (BV) is characterized by depletion of Lactobacillus and overgrowth of anaerobic and facultative bacteria, leading to increased mucosal inflammation, epithelial disruption, and poor reproductive health outcomes. However, the molecular mediators contributing to vaginal epithelial dysfunction are poorly understood. Here we utilized proteomic, transcriptomic and metabolomic analyses to characterize biological features underlying BV in 405 African women and explored functional mechanisms using bacterial co-culturesin vitro. We identified five major vaginal microbiome groups, (L.crispatus(21%), L.iners(18%), any non-specific Lactobacillus species(9%), Gardnerella species .vaginalis(30%), or polymicrobial(22%)). Using multi-‘omics we show that BV associated epithelial disruption and mucosal inflammation are linked to the mammalian target of rapamycin (mTOR) pathway and associate with Gardnerella.vaginalis, M.mulieris, and specific metabolites including imidazole propionate. Bacterial co-culturesExperiments in vitro confirmed that type strain G.vaginalis and, M.mulieris supernatants and, as well as, and imidazole propionate, directly affect epithelial barrier function and , accompanied by activation of mTOR pathways. These results establish the microbiome-mTOR axis as a central feature of epithelial dysfunction in BV.

2023-07-20 | PXD040895 | Pride

Vaginal epithelial dysfunction is mediated by the microbiome, metabolome, and mTOR signaling - Participant Group 2

Project description:Bacterial vaginosis (BV) is characterized by depletion of Lactobacillus and overgrowth of anaerobic and facultative bacteria, leading to increased mucosal inflammation, epithelial disruption, and poor reproductive health outcomes. However, the molecular mediators contributing to vaginal epithelial dysfunction are poorly understood. Here we utilized proteomic, transcriptomic and metabolomic analyses to characterize biological features underlying BV in 405 African women and explored functional mechanisms using bacterial co-cultures in vitro. We identified five major vaginal microbiome groups, (L.crispatus(21%), L.iners(18%), any non-specific Lactobacillus species(9%), Gardnerella species .vaginalis(30%), or polymicrobial(22%)). Using multi-‘omics we show that BV associated epithelial disruption and mucosal inflammation are linked to the mammalian target of rapamycin (mTOR) pathway and associate with Gardnerella.vaginalis, Mobiluncus mulieris, and specific metabolites including imidazole propionate. Bacterial co-culture experiments in vitro confirmed that type strain G.vaginalis and, M.mulieris supernatants as well as imidazole propionate, directly affect epithelial barrier function and are accompanied by activation of mTOR pathways. These results establish the microbiome-mTOR axis as a central feature of epithelial dysfunction in BV.

2023-07-20 | PXD040280 | Pride

Human vaginal metagenome

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Vaginal epithelial gene expression in postmenopausal women suffering from vaginal dryness

Project description:The onset of menopause is accompanied by a dramatic increase in reported symptoms of vaginal dryness, soreness, irritation or itching, pain with intercourse and bleeding after intercourse. Collectively these affect 25-50% of women of post-menopausal age and significantly impact their quality of life. To examine how gene expression differs between these groups, surface vaginal epithelial cells were collected from postmenopausal women suffering from vaginal dryness and appropriate controls not suffering from dryness. Affymetrix GeneChip Human 1.0 ST microarrays were performed on RNA isolated from ten participants.

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Vaginal epithelial gene expression in postmenopausal women suffering from vaginal dryness

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Global Expression of Molecular Transporters in the Human Vaginal Tract

Project description:Pre-exposure chemoprophylaxis using antiretroviral agents is a promising strategy for the prevention of sexual HIV transmission in women. Molecular transporters in the human vaginal tract may play a pivotal role in determining drug disposition and, consequently, pharmacodynamic outcomes in these efforts. Little is known, however, on the expression of these transporters in vaginal tissues, representing a critical knowledge gap. Our study analyzed the genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women undergoing gynecologic surgeries. The genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women (20-56 years old) undergoing gynecologic surgeries was measured.

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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.

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Differences in vaginal microbiota, host transcriptome and proteins in women with bacterial vaginosis are associated with metronidazole treatment response

Project description:Bacterial vaginosis (BV) treatment failures or recurrences are common. To identify features associated with treatment response, we compared vaginal microbiota and host ectocervical transcriptome before and after oral metronidazole therapy. Response to metronidazole is characterized by significant changes in chemokines and related transcripts suggesting that strategies to promote these pathways may prove beneficial.

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Micro-array analysis of the anterior vaginal wall from premenopausal patients with Pelvic Organ Prolapse (POP)

Project description:Pelvic organ prolapse (POP) is a common multifactorial disease in a heterogeneous population of women. Due to this heterogeneity, the underlying molecular mechanisms contributing to the pathogenesis of POP are still unclear. We sought to identify dysregulated pathways by comparing gene expression profiles of prolapsed and non- prolapsed anterior vaginal wall tissue within the same patient. Biopsies were collected from 12 premenopausal women undergoing prolapse surgery (cystocele POP-Q stage ≥ 2). A full thickness anterior vaginal wall sample was taken from the POP site during anterior colporrhaphy. An additional sample was taken from the non-prolapsed apex of the anterior vaginal cuff. Micro-array analysis was performed using whole genome GE 4x44K microarrays. Beside a significance analysis of micro-array (SAM), also a visual cluster analysis was performed. 12 women with POP: 12 biopsies anterior vaginal wall (POP site) versus 12 biopies precervical anterior vaginal wall ( non POP site)

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