-
Microbiology Spectrum Oct 2022Studies have confirmed that insomnia is related to gut microbiota. Previous research suggests that immunity and metabolism are also associated with insomnia. However, to...
Studies have confirmed that insomnia is related to gut microbiota. Previous research suggests that immunity and metabolism are also associated with insomnia. However, to our knowledge, the integration of these factors has not been investigated in insomnia. Here, we explored the correlations across gut microbiota, serum metabolism, and inflammatory factors in insomnia. Our results showed that the composition and structure of gut microbiota and metabolism in insomnia patients were different from healthy controls. Compared to healthy controls, the relative abundances of , Streptococcus, and Lactobacillus crispatus were significantly increased in insomniacs. There were five metabolic pathways in insomniacs (glycerophospholipid metabolism; glutathione metabolism; nitrogen metabolism; alanine, aspartate, and glutamate metabolism; aminoacyl-tRNA biosynthesis) significantly different between the two groups. Moreover, we found that IL-1β levels were significantly higher in insomnia patients while TNF-α was significantly reduced. We further identified that the changes in the level of IL-1β and TNF-α were associated with some specific bacteria and metabolites, such as Prevotella amnii, Prevotella buccalis, Prevotella timonensis, and Prevotella colorans. Mediation analysis further determined that the immune factors and metabolites could mediate the relationship between gut microbes and insomnia. Our study indicated that systematic inflammation and metabolites might be a pathway linking the gut microbiome with insomnia. These findings provide new insights and a better understanding of gut microbiota's role in insomnia as well as potential novel microbiome-related etiologies for insomnia.
Topics: Humans; Gastrointestinal Microbiome; Tumor Necrosis Factor-alpha; Sleep Initiation and Maintenance Disorders; Aspartic Acid; Alanine; Glycerophospholipids; Glutathione; Glutamates; Nitrogen; RNA, Transfer
PubMed: 36190400
DOI: 10.1128/spectrum.00998-22 -
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 -
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 -
Frontiers in Immunology 2023Bacterial vaginosis (BV) is a common infection of the lower genital tract with a vaginal microbiome dysbiosis caused by decreasing of lactobacilli. Previous studies... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
Bacterial vaginosis (BV) is a common infection of the lower genital tract with a vaginal microbiome dysbiosis caused by decreasing of lactobacilli. Previous studies suggested that supplementation with live may benefit the recovery of BV, however, the outcomes vary in people from different regions. Herein, we aim to evaluate the effectiveness of oral Chinese-origin with adjuvant metronidazole (MET) on treating Chinese BV patients. In total, 67 Chinese women with BV were enrolled in this parallel controlled trial and randomly assigned to two study groups: a control group treated with MET vaginal suppositories for 7 days and a probiotic group treated with oral TM13 and LG55 as an adjuvant to MET for 30 days. By comparing the participants with Nugent Scores ≥ 7 and < 7 on days 14, 30, and 90, we found that oral administration of probiotics did not improve BV cure rates (72.73% and 84.00% at day 14, 57.14% and 60.00% at day 30, 32.14% and 48.39% at day 90 for probiotic and control group respectively). However, the probiotics were effective in restoring vaginal health after cure by showing higher proportion of participants with Nugent Scores < 4 in the probiotic group compared to the control group (87.50% and 71.43% on day 14, 93.75% and 88.89% on day 30, and 77.78% and 66.67% on day 90). The relative abundance of the probiotic strains was significantly increased in the intestinal microbiome of the probiotic group compared to the control group at day 14, but no significance was detected after 30 and 90 days. Also, the probiotics were not detected in vaginal microbiome, suggesting that TM13 and LG55 mainly acted through the intestine. A higher abundance of at baseline was significantly associated with long-term cure failure of BV and greatly contributed to the enrichment of the lipid IVA synthesis pathway, which could aggravate inflammation response. To sum up, TM13 and LG55 can restore the vaginal health of patients recovering from BV, and individualized intervention mode should be developed to restore the vaginal health of patients recovering from BV.
CLINICAL TRIAL REGISTRATION
https://classic.clinicaltrials.gov/ct2/show/, identifier NCT04771728.
Topics: Female; Humans; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Lactobacillus; Lactobacillus crispatus; Lactobacillus gasseri; Metronidazole; Treatment Outcome; Vagina; Vaginosis, Bacterial
PubMed: 37575226
DOI: 10.3389/fimmu.2023.1125239 -
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 -
Frontiers in Cellular and Infection... 2022Preterm premature rupture of membranes (PPROM) is a common pregnancy complication. Yet, the main cause of PPROM remains poorly understood. In this study, we used 16S...
BACKGROUND
Preterm premature rupture of membranes (PPROM) is a common pregnancy complication. Yet, the main cause of PPROM remains poorly understood. In this study, we used 16S rRNA gene sequencing technology to identify the differences in vaginal microbiota between pregnant women with PPROM and those who delivered at term.
METHODS
Vaginal samples were collected from 48 patients with PPROM and 54 age- and gestational age-matched pregnant women who delivered at term (controls). The vaginal microbiota of the two groups was compared using 16S rRNA gene sequencing of the V3-V4 regions.
RESULTS
The vaginal microbial composition of the PPROM group was significantly different from that of the control group. Our results showed that the diversity of vaginal microbiota in patients with PPROM increased compared with controls. The relative abundance of sp., and were more abundant in patients with PPROM, while and were more abundant in controls. sp., and , could serve as biomarkers for PPROM. Finally, we proposed several metabolic pathways, including PWY-6339, PWY-6992, and PWY-7295.
CONCLUSION
PPROM is characterized by vaginal microbial dysbiosis. The dysbiotic vaginal microbiota signatures in patients with PPROM include a higher bacterial diversity, decreased autochthonous bacteria, and increased pathogenic bacteria. These results may be beneficial for developing biomarkers for screening and early diagnosis of PPROM and may provide effective preventative treatments.
Topics: Bacteria; Dysbiosis; Female; Fetal Membranes, Premature Rupture; Gardnerella vaginalis; Humans; Infant, Newborn; Microbiota; Pregnancy; Prevotella; RNA, Ribosomal, 16S; Vagina
PubMed: 36004326
DOI: 10.3389/fcimb.2022.858732 -
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 -
Frontiers in Microbiology 2022An association between the vaginal microbiome and preterm birth has been reported. However, in practice, it is difficult to predict premature birth using the microbiome...
An association between the vaginal microbiome and preterm birth has been reported. However, in practice, it is difficult to predict premature birth using the microbiome because the vaginal microbial community varies highly among samples depending on the individual, and the prediction rate is very low. The purpose of this study was to select markers that improve predictive power through machine learning among various vaginal microbiota and develop a prediction algorithm with better predictive power that combines clinical information. As a multicenter case-control study with 150 Korean pregnant women with 54 preterm delivery group and 96 full-term delivery group, cervicovaginal fluid was collected from pregnant women during mid-pregnancy. Their demographic profiles (age, BMI, education level, and PTB history), white blood cell count, and cervical length were recorded, and the microbiome profiles of the cervicovaginal fluid were analyzed. The subjects were randomly divided into a training ( = 101) and a test set ( = 49) in a two-to-one ratio. When training ML models using selected markers, five-fold cross-validation was performed on the training set. A univariate analysis was performed to select markers using seven statistical tests, including the Wilcoxon rank-sum test. Using the selected markers, including spp., , , , , and , machine learning models (logistic regression, random forest, extreme gradient boosting, support vector machine, and GUIDE) were used to build prediction models. The test area under the curve of the logistic regression model was 0.72 when it was trained with the 17 selected markers. When analyzed by combining white blood cell count and cervical length with the seven vaginal microbiome markers, the random forest model showed the highest test area under the curve of 0.84. The GUIDE, the single tree model, provided a more reasonable biological interpretation, using the 10 selected markers (, , , , , , , , , and ), and the covariates produced a tree with a test area under the curve of 0.77. It was confirmed that the association with preterm birth increased when and increased (AUC = 0.77), which could also be explained by the fact that as the number of increased, the association with preterm birth was high (AUC = 0.77). Our study demonstrates that several candidate bacteria could be used as potential predictors for preterm birth, and that the predictive rate can be increased through a machine learning model employing a combination of cervical length and white blood cell count information.
PubMed: 35983325
DOI: 10.3389/fmicb.2022.912853 -
Microorganisms Oct 2019The picture of dynamic interaction between oncogenic viruses and the vaginal bacteria-immune host milieu is incomplete. We evaluated the impact of , , and oncoviruses...
The picture of dynamic interaction between oncogenic viruses and the vaginal bacteria-immune host milieu is incomplete. We evaluated the impact of , , and oncoviruses on the vaginal Community State Types (CSTs) and host immune response in reproductive-age women. In our cohort, only and were detected and were associated with changes in the resident bacteria of CST I and IV ( < 0.05). increased in CST I while and increased in CST IV. Conversely, CST II and III showed an alteration of the immune response, with the decrease of Eotaxin, MCP-1, IL-7, IL-9, and IL-15 ( < 0.05), leading to reduced antiviral efficacy. An efficient viral clearance was observed only in women from CST I, dominated by . Our in vivo study begins to address the knowledge gap with respect to the role of vaginal bacteria and immune response in susceptibility to oncoviral infections.
PubMed: 31581600
DOI: 10.3390/microorganisms7100414