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The Journal of Infectious Diseases Apr 2024Dysbiosis of the vaginal microbiome poses a serious risk for sexual HIV-1 transmission. Prevotella spp. are abundant during vaginal dysbiosis and associated with...
Dysbiosis of the vaginal microbiome poses a serious risk for sexual HIV-1 transmission. Prevotella spp. are abundant during vaginal dysbiosis and associated with enhanced HIV-1 susceptibility; however, underlying mechanisms remain unclear. Here, we investigated the direct effect of vaginal bacteria on HIV-1 susceptibility of vaginal CD4+ T cells. Notably, pre-exposure to Prevotella timonensis enhanced HIV-1 uptake by vaginal T cells, leading to increased viral fusion and enhanced virus production. Pre-exposure to antiretroviral inhibitors abolished Prevotella timonensis-enhanced infection. Hence, our study shows that the vaginal microbiome directly affects mucosal CD4+ T cell susceptibility, emphasising importance of vaginal dysbiosis diagnosis and treatment.
PubMed: 38573164
DOI: 10.1093/infdis/jiae166 -
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 -
Genes Apr 2023Microbial Dysbiosis is associated with the etiology and pathogenesis of diseases. The studies on the vaginal microbiome in cervical cancer are essential to discern the...
Microbial Dysbiosis is associated with the etiology and pathogenesis of diseases. The studies on the vaginal microbiome in cervical cancer are essential to discern the cause and effect of the condition. The present study characterizes the microbial pathogenesis involved in developing cervical cancer. Relative species abundance assessment identified , , and dominating the phylum level. A significant increase in and at the species level revealed its pathogenic influence on cervical cancer progression. The diversity, richness, and dominance analysis divulges a substantial decline in cervical cancer compared to control samples. The β diversity index proves the homogeneity in the subgroups' microbial composition. The association between enriched at the species level, , , and genera with cervical cancer is identified by Linear discriminant analysis Effect Size (LEfSe) prediction. The functional enrichment corroborates the microbial disease association with pathogenic infections such as aerobic vaginitis, bacterial vaginosis, and chlamydia. The dataset is trained and validated with repeated k-fold cross-validation technique using a random forest algorithm to determine the discriminative pattern from the samples. SHapley Additive exPlanations (SHAP), a game theoretic approach, is employed to analyze the results predicted by the model. Interestingly, SHAP identified that the increase in Ralstonia has a higher probability of predicting the sample as cervical cancer. New evidential microbiomes identified in the experiment confirm the presence of pathogenic microbiomes in cervical cancer vaginal samples and their mutuality with microbial imbalance.
Topics: Humans; Female; Uterine Cervical Neoplasms; Dysbiosis; Microbiota; Artificial Intelligence
PubMed: 37107694
DOI: 10.3390/genes14040936 -
Reproductive Biomedicine Online Jun 2023What are the different features of the vaginal microbiome (VMB) between patients with polycystic ovary syndrome (PCOS) and healthy women?
RESEARCH QUESTION
What are the different features of the vaginal microbiome (VMB) between patients with polycystic ovary syndrome (PCOS) and healthy women?
DESIGN
A cross-sectional study was conducted at a single academic university-affiliated centre. A total of 1446 participants were recruited (PCOS group, n =713, control group, n = 733). Vaginal swabs were analysed using 16S rRNA gene sequencing. The diversity and composition of the microbiome were compared between the PCOS group and the control group. Microbial interaction networks and functional prediction were investigated.
RESULTS
The PCOS group had a higher alpha diversity than the control group (Shannon P = 0.03, Simpson P = 0.02), and higher intra-group variability was observed in PCOS group (P < 2.2E-16). At the genus level, the proportion of Lactobacillus decreased (85.1% versus 89.3%, false discovery rate [FDR] = 0.02), whereas the proportion of Gardnerella vaginalis and Ureaplasma increased in the PCOS group (5.1% versus 3.3%, FDR = 0.006; 1.2% versus 0.6%, FDR = 0.002, respectively). Lactobacillus acidophilus, Prevotella buccalis and G. vaginalis were identified as the main differential species. L. acidophilus was positively correlated with serum levels of anti-Müllerian hormone (AMH), and triglyceride (P = 2.01E-05, P = 0.004, respectively). P. buccalis was negatively correlated with serum levels of AMH and testosterone (P = 0.002, P = 0.003, respectively). G. vaginalis was positively correlated with serum levels of AMH, oestradiol and progesterone (P = 0.004, P = 0.005, P = 0.03, respectively). The VMB interaction network indicated that Lactobacillus crispus, Prevotella timonensis, and P. buccalis could be key drivers in the PCOS group. Overall, 55 predicted genes were found to be differentially abundant between PCOS and the control (FDRs < 0.25).
CONCLUSIONS
The PCOS group had a higher diversity of vaginal microbiome and showed an enhanced level of heterogeneity. The proportion of Lactobacillus in the PCOS group decreased, whereas the proportions of Gardnerella and Ureaplasma increased. These results warrant further research that can validate the correlation between PCOS and VMB.
Topics: Female; Humans; Polycystic Ovary Syndrome; Cross-Sectional Studies; RNA, Ribosomal, 16S; Anti-Mullerian Hormone; Microbiota
PubMed: 37085428
DOI: 10.1016/j.rbmo.2023.02.002 -
Applied and Environmental Microbiology May 2023d--hydroxyphenylglycine (d-HPG) is an important intermediate in the pharmaceutical industry. In this study, a tri-enzyme cascade for the production of d-HPG from l-HPG...
d--hydroxyphenylglycine (d-HPG) is an important intermediate in the pharmaceutical industry. In this study, a tri-enzyme cascade for the production of d-HPG from l-HPG was designed. However, the amination activity of Prevotella timonensis -diaminopimelate dehydrogenase (DAPDH) toward 4-hydroxyphenylglyoxylate (HPGA) was identified as the rate-limiting step. To overcome this issue, the crystal structure of DAPDH was solved, and a "binding pocket and conformation remodeling" strategy was developed to improve the catalytic activity toward HPGA. The best variant obtained, DAPDH, exhibited a catalytic efficiency (/) that was 26.75-fold higher than that of the wild type. This improvement was due to the enlarged substrate-binding pocket and enhanced hydrogen bond networks around the active center; meanwhile, the increased number of interdomain residue interactions drove the conformation distribution toward the closed state. Under optimal transformation conditions, DAPDH produced 19.8 g/L d-HPG from 40 g/L racemate DL-HPG in a 3 L fermenter within 10 h, with 49.5% conversion and >99% enantiomeric excess. Our study provides an efficient three-enzyme cascade pathway for the industrial production of d-HPG from racemate DL-HPG. d--hydroxyphenylglycine (d-HPG) is an important intermediate in the synthesis of antimicrobial compounds. d-HPG is mainly produced via chemical and enzymatic approaches, and enzymatic asymmetric amination employing diaminopimelate dehydrogenase (DAPDH) is considered an attractive method. However, the low catalytic activity of DAPDH toward bulky 2-keto acids limits its applications. In this study, we identified a DAPDH from Prevotella timonensis and created a mutant, DAPDH, which exhibited a catalytic efficiency (/) toward 4-hydroxyphenylglyoxylate that was 26.75-fold higher than that of the wild type. The novel strategy developed in this study has practical value for the production of d-HPG from inexpensive racemate DL-HPG.
Topics: Amination; Substrate Specificity
PubMed: 37070978
DOI: 10.1128/aem.00109-23 -
BMJ Open Respiratory Research Feb 2023Invasive pulmonary aspergillosis (IPA) remains underestimated in patients with community-acquired pneumonia (CAP). This study aims to describe clinical features and...
BACKGROUND
Invasive pulmonary aspergillosis (IPA) remains underestimated in patients with community-acquired pneumonia (CAP). This study aims to describe clinical features and outcomes of IPA in CAP patients, assess diagnostic performance of metagenomic next-generation sequencing (mNGS) for IPA and analyse lung microbiome via mNGS data.
METHODS
This retrospective cohort study included CAP patients from 22 April 2019 to 30 September 2021. Clinical and microbiological data were analysed. Diagnostic performance of mNGS was compared with traditional detection methods. The lung microbiome detected by mNGS was characterised and its association with clinical features was evaluated.
MAIN RESULTS
IPA was diagnosed in 26 (23.4%) of 111 CAP patients. Patients with IPA displayed depressed immunity, higher hospital mortality (30.8% vs 11.8%) and intensive care unit mortality (42.1% vs 17.5%) compared with patients without IPA. The galactomannan (GM) antigen test had the highest sensitivity (57.7%) in detecting the spp, followed by mNGS (42.3%), culture (30.8%) and smear (7.7%). The mNGS, culture and smear had 100% specificity, while GM test had 92.9% specificity. The microbial structure of IPA significantly differed from non-IPA patients (p<0.001; Wilcoxon test). Nineteen different species were significantly correlated with clinical outcomes and laboratory biomarkers, particularly for , and .
CONCLUSIONS
Our results reveal that patients with infection tend to have a higher early mortality rate. The mNGS may be suggested as a complement to routine microbiological test in diagnosis of patients at risk of infection. The lung microbiota is associated with inflammatory, immune and metabolic conditions of IPA, and thus influences clinical outcomes.
Topics: Humans; Invasive Pulmonary Aspergillosis; Retrospective Studies; Sensitivity and Specificity; Bronchoalveolar Lavage Fluid; Aspergillosis; Lung; Pneumonia; Microbiota
PubMed: 36828645
DOI: 10.1136/bmjresp-2022-001358 -
Biology Dec 2022Background: The vaginal microbiome is closely associated with the onset and recurrence of bacterial vaginosis (BV). In the present study, the state of vaginal microbiota...
Background: The vaginal microbiome is closely associated with the onset and recurrence of bacterial vaginosis (BV). In the present study, the state of vaginal microbiota during the onset and post-treatment asymptomatic stages of BV were compared to that of a healthy population to evaluate the changes in different characteristic bacteria during the onset, progression, and remission of BV. Methods: A case−control study was performed to explore these changes. Women with clinical symptoms of BV were divided into the disease group (M) and case−control group (C) based on the Nugent score. Subjects in the disease group whose symptoms were resolved after the treatment were assigned to the treated group (T) and healthy subjects were recruited into the normal control (N) group. The V3−V4 hypervariable regions of bacterial 16S rRNA genes were sequenced on the Illumina MiSeq platform. Results: The N harbored the highest number of detected species and a higher abundance of microbiota; they had a significantly higher abundance of Lactobacillus and different bacterial community composition compared to the other three groups. In group M, Gardnerella vaginalis was the dominant species, whereas Lactobacillus iners was predominant in the other three groups. While Lactobacillus was more commonly present in Group C compared to group M. it was significantly increased in group T. Alpha diversity analysis of bacterial communities revealed significant differences in community richness and diversity among all four groups (p < 0.05). Significant differences in the distribution of various bacterial communities among the different groups were also observed (p < 0.05). Specifically, the abundance of eight bacterial taxa (Megasphaera, Aerococcus christensenii, Clostridiales, Gardnerella, Peptostreptococcus, Veillonellaceae, Akkermansia, Coriobacteriales) differed significantly among the four groups (p < 0.05). Conclusion: Significant differences in the composition and alpha diversity of the vaginal microbiota at different stages of BV and the distribution of bacterial communities were observed among the investigated groups. In addition to Gardnerella, Sneathia sanguinegens and Prevotella timonensis play an important role in the pathogenesis of BV. The appearance of BV-like clinical symptoms was closely associated with the decrease in Prevotella and Atopobium vaginae populations.
PubMed: 36552306
DOI: 10.3390/biology11121797 -
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 -
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 -
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