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The EMBO Journal Oct 2022Dysbiosis of vaginal microbiota is associated with increased HIV-1 acquisition, but the underlying cellular mechanisms remain unclear. Vaginal Langerhans cells (LCs)...
Dysbiosis of vaginal microbiota is associated with increased HIV-1 acquisition, but the underlying cellular mechanisms remain unclear. Vaginal Langerhans cells (LCs) protect against mucosal HIV-1 infection via autophagy-mediated degradation of HIV-1. As LCs are in continuous contact with bacterial members of the vaginal microbiome, we investigated the impact of commensal and dysbiosis-associated vaginal (an)aerobic bacterial species on the antiviral function of LCs. Most of the tested bacteria did not affect the HIV-1 restrictive function of LCs. However, Prevotella timonensis induced a vast uptake of HIV-1 by vaginal LCs. Internalized virus remained infectious for days and uptake was unaffected by antiretroviral drugs. P. timonensis-exposed LCs efficiently transmitted HIV-1 to target cells both in vitro and ex vivo. Additionally, P. timonensis exposure enhanced uptake and transmission of the HIV-1 variants that establish infection after sexual transmission, the so-called Transmitted Founder variants. Our findings, therefore, suggest that P. timonensis might set the stage for enhanced HIV-1 susceptibility during vaginal dysbiosis and advocate targeted treatment of P. timonensis during bacterial vaginosis to limit HIV-1 infection.
Topics: Antiviral Agents; Dysbiosis; Female; HIV Infections; HIV-1; Humans; Langerhans Cells; Prevotella
PubMed: 35968812
DOI: 10.15252/embj.2022110629 -
PloS One 2022Bacterial vaginosis (BV) is associated with a state of vaginal dysbiosis typically involving depletion of otherwise dominant populations of Lactobacillus. The causes of...
Association of key species of vaginal bacteria of recurrent bacterial vaginosis patients before and after oral metronidazole therapy with short- and long-term clinical outcomes.
Bacterial vaginosis (BV) is associated with a state of vaginal dysbiosis typically involving depletion of otherwise dominant populations of Lactobacillus. The causes of this microbial succession are not known; there may be multiple causes. Standard treatment includes oral metronidazole, which typically restores Lactobacillus species to dominance. However, recurrence rates are high; recurrent BV patients recur 3-4 times annually and are often refractory to treatment. Our previous qPCR-based study of recurrent BV patients pointed to putatively more virulent species of Gardnerella that were associated with refractory responses to oral metronidazole, and less robust recovery of Lactobacillus species associated with recurrence after an initial period of remission. However, these associations did not account for outcomes in all patients, suggesting that other bacterial species were involved. In this follow-up study, we sequenced the V4 domain of 16S rRNA sequences of 41of these same patients pre- and posttreatment. Overall compositions among pretreatment clinical outcome groups were not different, although alpha diversity significantly decreased: refractory > recurrent > remission. Combinations of key species were associated with and prognostic for outcome. Higher pretreatment abundance of Megasphaera lornae together with lower abundance of Gardnerella Gsp07 and Finegoldia magna predicted long term remission after oral metronidazole. Furthermore, a subset of refractory patients that did not have high levels of Gardnerella Gsp07, instead had elevated levels of alternative species including Atopobium vaginae, Mageeibacillus indolicus (BVAB3), and Prevotella timonensis. Patients who recurred after transient remission had elevated abundance of species including Atopobium vaginae, Gardnerella, and Aerococcus christensenii, compared to long-term remission patients. Core bacterial species among refractory patients did not change in abundance after metronidazole, suggesting resistance or tolerance, in contrast to the loss in abundance of the same species among recurrent or remission patients. These findings have potential prognostic and therapeutic implications.
Topics: Actinobacteria; Bacteria; Female; Follow-Up Studies; Gardnerella vaginalis; Humans; Lactobacillus; Metronidazole; RNA, Ribosomal, 16S; Vagina; Vaginosis, Bacterial
PubMed: 35901180
DOI: 10.1371/journal.pone.0272012 -
Biomedicine & Pharmacotherapy =... May 2022New means to stabilize the microbial balance during pregnancy could benefit maternal health. Our objectives were to investigate in overweight/obese pregnant women 1) the... (Randomized Controlled Trial)
Randomized Controlled Trial
New means to stabilize the microbial balance during pregnancy could benefit maternal health. Our objectives were to investigate in overweight/obese pregnant women 1) the impact of long-chain polyunsaturated fatty acids (fish oil) and/or probiotics on the vaginal microbiota, 2) its relation to gestational diabetes mellitus (GDM) and 3) its interaction with vaginal active matrix metalloproteinase-8 (aMMP-8) and serum high sensitivity C-reactive protein (hsCRP) and phosphorylated insulin-like growth factor-binding protein-1 (phIGFBP-1), IGFBP-1 and aMMP-8. The women were allocated to fish oil + placebo, probiotics + placebo, fish oil + probiotics and placebo + placebo-groups, from early pregnancy onwards (fish oil: 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid; probiotics: Lacticaseibacillus rhamnosus HN001 (formerly Lactobacillus rhamnosus HN001) and Bifidobacterium animalis ssp. lactis 420, 10 colony-forming units each). Vaginal and serum samples (early pregnancy, n = 112; late pregnancy, n = 116), were analyzed for vaginal microbiota using 16S rRNA gene amplicon sequencing and vaginal aMMP-8 and serum hsCRP, aMMP-8, phIGFBP-1 and IGFBP-1 by immunoassays. GDM was diagnosed from a 2-h 75 g OGTT. ClinicalTrials.gov, NCT01922791. The intervention exerted effects on many low-abundant bacteria. Compared to the placebo-group, there was a lower abundance of potential pathobionts, namely Ureaplasma urealyticum in the fish oil-group, Ureaplasma, U. urealyticum and Prevotella disiens in the probiotics-group, Dialister invisus and Prevotella timonensis in the fish oil + probiotics-group. Moreover, probiotics decreased the abundance of a few potential pathobionts during pregnancy. Many bacteria were related to GDM. The vaginal aMMP-8 level correlated significantly with α-diversity and inversely with two Lactobacillus species. Dietary interventions, especially probiotics, may have beneficial effects on the vaginal microbiota during pregnancy.
Topics: Bifidobacterium animalis; C-Reactive Protein; Diabetes, Gestational; Female; Fish Oils; Humans; Insulin-Like Growth Factor Binding Protein 1; Lacticaseibacillus rhamnosus; Microbiota; Obesity; Overweight; Pregnancy; Pregnant Women; Probiotics; RNA, Ribosomal, 16S
PubMed: 35344737
DOI: 10.1016/j.biopha.2022.112841 -
The Journal of Infectious Diseases Jun 2022A 25-mg dapivirine vaginal ring has been demonstrated to reduce risk of human immunodeficiency virus (HIV) acquisition in nonpregnant adult women. In this secondary...
BACKGROUND
A 25-mg dapivirine vaginal ring has been demonstrated to reduce risk of human immunodeficiency virus (HIV) acquisition in nonpregnant adult women. In this secondary analysis of studies conducted in US adolescent, lactating, and postmenopausal females, vaginal microbiota was assessed prior to and after ring use, and between dapivirine and placebo ring users.
METHODS
Vaginal fluid swabs were collected before and after product use for the evaluation of microbiota using Nugent criteria, quantitative culture, and quantitative polymerase chain reaction.
RESULTS
Vaginal ring use did not impact bacterial vaginosis prevalence among the 3 populations and was associated with minimal shifts in microbiota. Adolescents in both arms demonstrated an increased prevalence of Lactobacillus crispatus and a decrease in quantity of Megasphaera lornae. Postmenopausal active and placebo ring users demonstrated an increased prevalence of lactobacilli and non-albicans yeast, while dapivirine ring users demonstrated an increased prevalence of Candida albicans and increased quantity of group B Streptococcus and non-albicans yeasts. Prevotella species were increased in lactating women, whereas Prevotella timonensis increased in prevalence and concentration among adolescent and postmenopausal females and Prevotella bivia increased in prevalence among adolescent dapivirine ring users.
CONCLUSIONS
Dapivirine vaginal ring use was associated with minimal changes in the vaginal microbiota that are likely not clinically significant.
Topics: Adolescent; Adult; Contraceptive Devices, Female; Female; Humans; Lactation; Microbiota; Postmenopause; Pyrimidines; Vagina
PubMed: 34865071
DOI: 10.1093/infdis/jiab590 -
Microbiome May 2021Obesity and vaginal microbiome (VMB) dysbiosis are each risk factors for adverse reproductive and oncological health outcomes in women. Here, we investigated the...
BACKGROUND
Obesity and vaginal microbiome (VMB) dysbiosis are each risk factors for adverse reproductive and oncological health outcomes in women. Here, we investigated the relationship between obesity, vaginal bacterial composition, local inflammation and bariatric surgery.
METHODS
Vaginal bacterial composition assessed by high-throughput sequencing of bacterial 16S rRNA genes and local cytokine levels measured using a multiplexed Magnetic Luminex Screening Assay were compared between 67 obese and 42 non-obese women. We further assessed temporal changes in the microbiota and cytokines in a subset of 27 women who underwent bariatric surgery.
RESULTS
The bacterial component of the vaginal microbiota in obese women was characterised by a lower prevalence of a Lactobacillus-dominant VMB and higher prevalence of a high diversity (Lactobacillus spp., and Gardnerella- spp. depleted) VMB, compared with non-obese subjects (p<0.001). Obese women had higher relative abundance of Dialister species (p<0.001), Anaerococcus vaginalis (p=0.021), and Prevotella timonensis (p=0.020) and decreased relative abundance of Lactobacillus crispatus (p=0.014). Local vaginal IL-1β, IL-4, IL-6, IL-8, IFNγ, MIP-1α and TNFα levels were all higher among obese women, however, only IL-1β and IL-8 correlated with VMB species diversity. In a subset of obese women undergoing bariatric surgery, there were no significant overall differences in VMB following surgery; however, 75% of these women remained obese at 6 months. Prior to surgery, there was no relationship between body mass index (BMI) and VMB structure; however, post-surgery women with a Lactobacillus-dominant VMB had a significantly lower BMI than those with a high diversity VMB.
CONCLUSIONS
Obese women have a significantly different vaginal microbiota composition with increased levels of local inflammation compared to non-obese women. Bariatric surgery does not change the VMB; however, those with the greatest weight loss 6-month post-surgery are most likely to have a Lactobacillus-dominant VMB. Video abstract.
Topics: Bariatric Surgery; Female; Firmicutes; Humans; Microbiota; Obesity; Prevotella; RNA, Ribosomal, 16S; Vagina; Weight Loss
PubMed: 34049596
DOI: 10.1186/s40168-021-01011-2 -
PloS One 2020To evaluate the changes of vaginal microbiota during cervical carcinogenesis in women with high-risk human papillomavirus infection.
OBJECTIVE
To evaluate the changes of vaginal microbiota during cervical carcinogenesis in women with high-risk human papillomavirus infection.
MATERIALS AND METHODS
Vaginal microbiota was analyzed using next-generation sequencing in women with normal, cervical intraepithelial neoplasia (CIN), or cervical cancer.
RESULTS
A marked decrease of Lactobacillus crispatus was found in the CIN/cancer groups compared with that in the normal group. The diversity of microorganisms increased in patients with CIN or cervical cancer with HPV infection. Atopobium vaginae (OR 4.33, 95% CI 1.15-16.32), Dialister invisus (OR 4.89, 95% CI 1.20-19.94), Finegoldia magna (OR 6.00, 95% CI 1.08-33.27), Gardnerella vaginalis (OR 7.43, 95% CI 1.78-31.04), Prevotella buccalis (OR 11.00, 95% CI 2.00-60.57), and Prevotella timonensis (OR 6.00, 95% CI 1.46-24.69) were significantly associated with the risk of CIN 2/3 or cervical cancer.
CONCLUSION
Women with the CIN and cervical cancer showed a high diversity in vaginal microbiota. Depletion of Lactobacillus crispatus and increased abundance of anaerobic bacteria were detected in women with cervical disease.
Topics: Bacteria; Biodiversity; Carcinogenesis; Female; Humans; Microbiota; Papillomaviridae; Papillomavirus Infections; Principal Component Analysis; Species Specificity; Vagina
PubMed: 32941440
DOI: 10.1371/journal.pone.0238705 -
BMC Infectious Diseases Aug 2020In this study, the association between human papillomavirus (HPV) infection and related cervical intraepithelial neoplasia (CIN) or cervical cancer and vaginal...
BACKGROUND
In this study, the association between human papillomavirus (HPV) infection and related cervical intraepithelial neoplasia (CIN) or cervical cancer and vaginal microbiome was evaluated in Chinese cohorts.
METHODS
The vaginal bacterial composition of five groups, HPV-infected women without CINs (HPV, n = 78), women with low-grade squamous intraepithelial lesions (LSIL, n = 51), women with high-grade squamous intraepithelial lesions (HSIL, n = 23), women with invasive cervical cancer (Cancer, n = 9) and healthy women without HPV infection (Normal, n = 68), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3-4) using Illumina MiSeq.
RESULTS
HPV infection increased vaginal bacterial richness and diversity regardless of the status of CINs. The vaginal bacterial richness and diversity were further augmented in women with cervical cancer. Lactobacillus was the most abundant genus in all groups. HPV infection had a negative influence on the abundances of Lactobacillus, Gardnerella and Atopobium. Accordingly, HPV infection increased the relative abundance of Prevotella, Bacillus, Anaerococcus, Sneathia, Megasphaera, Streptococcus and Anaerococcus. The increased proportions of Bacillus, Anaerococcus and the reduced abundance of Gradnerella vaginalis were probably related with the progression of CINs severity. HPV infection without CINs or cancerous lesions was strongly associated with Megasphaera. The most abundant bacterium in the LSIL group was Prevotella amnii. However, Prevotella timonensis, Shuttleworthia and Streptococcaceae at the family level were three taxa related to HSIL. Furthermore, more taxa were associated with the Cancer group including Bacillus, Sneathia, Acidovorax, Oceanobacillus profundus, Fusobacterium, Veillonellaceae at the family level, Anaerococcus and Porphyromonas uenonis. Samples in the Normal group were mostly assigned to CST III. HPV infection converted the vaginal bacterial community structure from CST III to CST IV. Furthermore, the proportions of CST IV were gradually augmented with the progression of the severity of CINs.
CONCLUSIONS
This work interpreted the differential vaginal bacteria under HPV infection and various precancerous or cancerous lesions in a Chinese cohort. We distinguished the specific microbes and the vaginal bacterial structure that were related with the progression of CINs severity in Chinese women.
Topics: Adult; Aged; Biodiversity; China; Cohort Studies; Disease Progression; Female; Humans; Lactobacillus; Microbiota; Middle Aged; Papillomaviridae; Papillomavirus Infections; RNA, Ribosomal, 16S; Uterine Cervical Neoplasms; Vagina; Uterine Cervical Dysplasia
PubMed: 32842982
DOI: 10.1186/s12879-020-05324-9 -
Microorganisms Jun 2020Vaginal microbiota dysbiosis and bacterial vaginosis (BV) affect negatively women's health. Understanding vaginal microbiota fluctuations in BV during and after...
Vaginal microbiota dysbiosis and bacterial vaginosis (BV) affect negatively women's health. Understanding vaginal microbiota fluctuations in BV during and after antibiotic treatment would facilitate accurate decision-making on the treatment regimen, avoid unnecessary antibiotic use, and potentially mitigate recurrence. We investigated vaginal microbiota composition of 30 women with BV before and after 5-day metronidazole treatment and compared the results with 30 healthy women. Vaginal microbiota was assessed by Nugent score and analyzed by 16S rRNA gene sequencing in swabs on baseline Day 1, and on Day 8 and 15, after completion of antibiotic treatment by women with BV. Prior to antibiotic treatment (Day 1), BV-positive women were dominated by (25.8%), (18.0%), and (14.6%), whereas healthy women were dominated by (37.5%) and (19.2%). On Day 8, abundance increased in BV-treated women being significantly higher compared with healthy women (67.8% vs. 37.5%, = 0.049). On Day 15, the relative abundance of all microbial taxa was similar between the groups. Vaginal microbiota of women with BV shifted to resemble that of healthy controls after metronidazole. Sequencing analysis provides more in-depth understanding of changes in vaginal microbiota. The role of in vaginal health and dysbiosis requires further investigations.
PubMed: 32527048
DOI: 10.3390/microorganisms8060875 -
Nature Communications Apr 2020Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia...
Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN); however, causal inference remains uncertain. Here, we use bacterial DNA sequencing from serially collected vaginal samples from a cohort of 87 adolescent and young women aged 16-26 years with histologically confirmed, untreated CIN2 lesions to determine whether VMB composition affects rates of regression over 24 months. We show that women with a Lactobacillus-dominant microbiome at baseline are more likely to have regressive disease at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression. These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies.
Topics: Adolescent; Adult; Cervix Uteri; Cohort Studies; DNA, Bacterial; Female; Follow-Up Studies; Gardnerella vaginalis; Humans; Lactobacillus; Microbiota; Neoplasm Staging; Papillomaviridae; Papillomavirus Infections; Prevotella; RNA, Ribosomal, 16S; Risk Factors; Uterine Cervical Neoplasms; Vagina; Young Adult; Uterine Cervical Dysplasia
PubMed: 32332850
DOI: 10.1038/s41467-020-15856-y -
Journal of Reproductive Immunology Apr 2020Dysbiosis of the vaginal microbiome as a result of overgrowth of anaerobic bacteria leads to bacterial vaginosis (BV) which is associated with increased inflammation in...
Dysbiosis of the vaginal microbiome as a result of overgrowth of anaerobic bacteria leads to bacterial vaginosis (BV) which is associated with increased inflammation in the genital mucosa. Moreover, BV increases susceptibility to sexual transmitted infections (STIs) and is associated with adverse pregnancy outcomes. It remains unclear how specific vaginal aerobic and anaerobic bacteria affect health and disease. We selected different vaginal bacteria ranging from true commensals to species associated with dysbiosis and investigated their effects on activation of dendritic cells (DCs). Commensal Lactobacilli crispatus did not induce DC maturation nor led to production of pro-inflammatory cytokines. In contrast, BV-associated bacteria Megasphaera elsdenii and Prevotella timonensis induced DC maturation and increased levels of pro-inflammatory cytokines. Notably, DCs stimulated with Prevotella timonensis suppressed Th2 responses and induced Th1 skewing, typically associated with preterm birth. In contrast, Lactobacillus crispatus and Megasphaera elsdenii did not affect Th cell polarization. These results strongly indicate that the interaction of vaginal bacteria with mucosal DCs determines mucosal inflammation and we have identified the anaerobic bacterium Prevotella timonensis as a strong inducer of inflammatory responses. Specifically targeting these inflammation-inducing bacteria might be a therapeutic strategy to prevent BV and associated risks in STI susceptibility and preterm birth.
Topics: Cells, Cultured; Cytokines; Dendritic Cells; Dysbiosis; Female; Humans; Inflammation Mediators; Leukocytes, Mononuclear; Megasphaera elsdenii; Prevotella; Primary Cell Culture; Vagina; Vaginosis, Bacterial
PubMed: 32004804
DOI: 10.1016/j.jri.2020.103085