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.
2021-05-21 | GSE174799 | GEO
Project description:EMG produced TPA metagenomics assembly of PRJNA669294 data set (Effect of metronidazole on vaginal microbiota associated with asymptomatic bacterial vaginosis).
Project description:The hormonal contraceptive medroxyprogesterone acetate (MPA) is associated with increased risk of human immunodeficiency virus (HIV), via incompletely understood mechanisms. Increased diversity in the vaginal microbiota modulates genital inflammation and is associated with increased HIV-1 acquisition. However, the effect of MPA on diversity of the vaginal microbiota is relatively unknown. In a cohort of female Kenyan sex workers, negative for sexually transmitted infections (STIs), with Nugent scores <7 (N=58 of 370 screened), MPA correlated with significantly increased diversity of the vaginal microbiota as assessed by 16S rRNA gene sequencing. MPA was also significantly associated with decreased levels of estrogen in the plasma, and low vaginal glycogen and α-amylase, factors implicated in vaginal colonization by lactobacilli, bacteria that are believed to protect against STIs. In a humanized mouse model, MPA treatment was associated with low serum estrogen, low glycogen and enhanced HIV-1 susceptibility. The mechanism by which the MPA mediated changes in the vaginal microbiota may contribute to HIV-1 susceptibility in humans appears to be independent of inflammatory cytokines and/or activated T cells. Altogether, these results suggest MPA-induced hypo-estrogenism may alter key metabolic components that are necessary for vaginal colonization by certain bacterial species including lactobacilli, and allow for greater bacterial diversity in the vaginal microbiota.
Project description:Differences in vaginal microbiota, host transcriptome and proteins in women with bacterial vaginosis are associated with metronidazole treatment response
Project description:Differences in vaginal microbiota, host transcriptome and proteins in women with bacterial vaginosis are associated with metronidazole treatment response
Project description:Instability in the composition of gut bacterial communities, referred as dysbiosis, has been associated with important human intestinal disorders such as CrohnM-bM-^@M-^Ys disease and colorectal cancer. Here, we show that dysbiosis coupled to Nod2 or Rip2 deficiency suffices to cause an increased risk for intestinal inflammation and colitis-associated carcinogenesis in mice. Aggravated epithelial lesions and dysplasia upon chemical-induced injury associated with loss of Nod2 or Rip2 can be prevented by antibiotics or anti-IL6R treatment. Nod2-mediated risk for intestinal inflammation and colitis-associated tumorigenesis is communicable through maternally-transmitted microbiota even to wild-type hosts. Disease progression was identified to drive complex NOD2-dependent changes of the colonic-associated microbiota. Reciprocal microbiota transplantation rescues the vulnerability of Nod2-deficient mice to colonic injury. Altogether, our results unveil an unexpected function for NOD2 in shaping a protective assembly of gut microbial communities, providing a rationale for intentional manipulation of genotype-dependent dysbiosis as a causative therapeutic principle in chronic intestinal inflammation. Analysis used RNA extracted from colonic mucosa of untreated, antibiotics-treated or metronidazole-treated C57Bl/6J and Nod2-deficient mice in CAC model. Direct comparisons were performed as follow: C57Bl/6J untreated mice vs Nod2-deficient untreated mice, C57Bl/6J antibiotics-treated mice vs Nod2-deficient antibiotics-treated mice, C57Bl/6J metronidazole-treated mice vs Nod2-deficient metronidazole-treated mice, C57Bl/6J untreated mice vs C57Bl/6J antibiotics-treated mice, C57Bl/6J untreated mice vs C57Bl/6J metronidazole-treated mice, Nod2-deficient untreated mice vs Nod2-deficient antibiotics-treated mice, Nod2-deficient untreated mice vs Nod2-deficient metronidazole-treated mice. Indirect comparisons with control data were made across multiple arrays with raw data pulled from different channels for data analysis.
Project description:<p>Preterm birth is the leading cause of neonatal morbidity and mortality. A failure to predict and understand the causes of preterm birth have limited effective interventions and therapeutics. From a cohort of 2,000 pregnant women, we performed a nested case control study on 107 well-phenotyped cases of spontaneous preterm birth (sPTB) and 432 women delivering at term. Modern and innovative Bayesian modeling of vaginal microbiota identified features of these communities associated with PTB. Seven bacterial taxa were shown to have relative abundances significantly associated with an increased risk of sPTB, with a stronger effect in African American women. However, higher vaginal levels of β-defensins significantly decreased the risk of sPTB associated with the vaginal microbiota in an ethnicity-dependent manner. These findings hold promise for the development of novel diagnostics that could more accurately identify women at risk for sPTB early in pregnancy and offer new therapeutic strategies that would include immune modulators and microbiome-based therapeutics to reduce this significant health burden.</p>
| phs001739 | dbGaP
Project description:Fecal and vaginal microbiota after probiotic treatment for bacterial vaginosis
Project description:<p>Archived self-collected vaginal swabs were utilized from a pilot study of vaginal douching cessation (NIH/NIAID R03-AI061131). Thirty-nine non-pregnant, reproductive-age women who reported the use of vaginal douche products in the two months prior to screening were enrolled. Thirty-three of these successfully completed the 16-week longitudinal study. Participants self-collected vaginal swabs and smears twice weekly. We report sequences based on the analysis of 16S rRNA gene sequences amplified from whole genomic DNA isolated from the swabs. Bacterial vaginosis (BV) is defined by Gram's stain of vaginal fluid (Nugent's score ≥7).</p> <p>The large body of information generated will facilitate understanding of vaginal microbial community dynamics, the etiology of BV, and drive the development of better diagnostic tools for BV. Furthermore, it is hoped that the information will enable a more personalized treatment of BV and ultimately, prevent adverse sequelae associated with BV.</p>
| phs000261 | dbGaP
Project description:Vaginal viromes of a Bacterial Vaginosis Patient