Longitudinal analysis reveals characteristically high proportions of bacterial vaginosis-associated bacteria and temporal variability of vaginal microbiota in northern pig-tailed macaques （Macaca leonina）

The complex and dynamic vaginal microbial ecosystem is critical to both health and disease of the host. Studies focusing on how vaginal microbiota influences HIV-1 infection may face limitations in selecting proper animal models. Given that northern pig-tailed macaques （Macaca leonina） are susceptible to HIV-1 infection, they may be an optimal animal model for elucidating the mechanisms by which vaginal microbiota contributes to resistance and susceptibility to HIV-1 infection. However, little is known about the composition and temporal variability of vaginal microbiota of the northern pig-tailed macaque. Here, we present a comprehensive catalog of the composition and temporal dynamics of vaginal microbiota of two healthy northern pig-tailed macaques over 19 weeks using 454-pyrosequencing of 16S rRNA genes. We found remarkably high proportions of a diverse array of anaerobic bacteria associated with bacterial vaginosis. Atopobium and Sneathia were dominant genera, and interestingly, we demonstrated the presence of Lactobacillus-dominated vaginal microbiota. Moreover, longitudinal analysis demonstrated that the temporal dynamics of the vaginal microbiota were considerably individualized. Finally, network analysis revealed that vaginal pH may influence the temporal dynamics of the vaginal microbiota, suggesting that inter-subject variability of vaginal bacterial communities could be mirrored in inter-subject variation in correlation profiles of species with each other and with vaginal pH over time. Our results suggest that the northern pig-tailed macaque could be an ideal animal model for prospective investigation of the mechanisms by which vaginal microbiota influence susceptibility and resistance to HIV-1 infection in the context of highly polymicrobial and Lactobacillus-dominated states.

Influence of group B streptococcus and vaginal cleanliness on the vaginal microbiome of pregnant women

BACKGROUND The vaginal microbiome plays a critical role in the health of pregnant women and their newborns.Group B Streptococcus(GBS)and vaginal cleanliness significantly affect the vaginal microecosystem and are closely associated with vaginal diseases.AIM To explore the effects of GBS status and vaginal cleanliness on vaginal microecosystems.METHODS We collected 160 vaginal swabs from pregnant women and divided them into the following four groups based on GBS status and vaginal cleanliness:GBS-positive+vaginal cleanliness I–II degree,GBS-negative+vaginal cleanliness I–II degree,GBS-positive+vaginal cleanliness III–IV degree,and GBS-negative+vaginal cleanliness III–IV degree.Samples were subjected to 16S rRNA gene amplicon sequencing.RESULTS Alpha diversity analysis showed that the Shannon index did not significantly differ between the four groups.We identified significant variation in taxa abundance between the GBS-positive and GBS-negative groups and between the vaginal cleanliness I–II degree and III–IV degree groups.Principal coordinate analysis and non-metric multidimensional scaling analysis further confirmed the microbial diversity of the four groups.Moreover,the linear discriminant analysis demonstrated that Lactobacillus jensenii and Actinobacteria were strongly associated with GBS-positive status,and Lactobacillus iners,Lactobacillaceae,Lactobacillus,Lactobacillales,Bacilli and Firmicutes were closely correlated with GBS-negative status.CONCLUSION GBS status and vaginal cleanliness significantly affect vaginal microbiome differences in pregnant women.Our findings provide instructional information for clinical antibiotic treatment in pregnant women with different GBS statuses and vaginal cleanliness degrees.

The Utility of Voided Urine Samples as a Proxy for the Vaginal Microbiome and for the Prediction of Bacterial Vaginosis

Recent work has shown that the vaginal microbiome exerts a strong impact on women's gynecological health.However,collection of vaginal specimens is invasive and requires previous clinical training or the involvement of a trained clinician.In contrast,urine sample collection is routine and noninvasive and does not require involvement of a clinician.We sought to compare the vaginal and urogenital microbiomes to assess the utility of voided urine samples as a proxy for the vaginal microbiome.Paired urogenital and vaginal samples were collected from pregnant women and characterized by 16S rRNA taxonomic profiling.We examined diversities and compositions of paired urogenital and vaginal microbiomes using five discrete strategies to explore the similarity between the vaginal and urogenital microbiomes.A strategy comparing the paired urogenital and vaginal microbiomes in which taxa were assigned using the STIRRUPS database and urine-specific taxa were removed showed no significant difference in diversity and composition between the paired urogenital and vaginal microbiomes.Moreover,the relative abundances of common vaginal taxa were linearly correlated with those in the paired urogenitalmicrobiomes.These similarities suggest that voided urine samples could represent a noninvasive protocol for accurate profiling of the vaginalmicrobiome with likely clinical applications.Finally,a machine learning model was established in which the voided urine microbiome was compared favorably to the vaginal microbiome in predicting bacterial vaginosis.

Comparative metagenomic analysis of the vaginal microbiome in healthy women

The composition of these vaginal microbiome has a significant impact on women’s health.However,few studies have characterized the vaginal microbiome of healthy Chinese women using metagenomic sequencing.Here,we carried out a comparative metagenomic analysis to survey taxonomic,functional levels,and microbial communities’genome content in healthy women’s vaginal microbiome.Overall,we observed a total of 111 species,including all dominant vaginal Lactobacillus species,such as L.iners,L.crispatus,L.gasseri,and L.jensenii.Unlike microbial taxa,several pathways were ubiquitous and prevalent across individuals,including adenosine ribonucleotides de novo biosynthesis and pyruvate fermentation to acetate and lactate Ⅱ.Notably,our diversity analysis confirmed a significant difference in healthy women from different ethnic groups.Moreover,we binned vaginal assemblies into 62 high-quality genomes,including 9 L.iners,7 A.vaginae,5 L.jensenii,and 5 L.crispatus.We identified the pan and core genomes of L.iners and A.vaginae and revealed the genetic diversity.Primary differences between strains were the hypothetical genes and mobile element-like genes.Our results provide a framework for understanding the implications of the female reproductive tract’s composition and functional potential and highlight the importance of genome-resolved metagenomic analysis to further understand the human vaginal microbiome.

Multi-omic Microbiome Profiles in the Female Reproductive Tract in Early Pregnancy

The vaginal microbiome likely influences host signaling compounds within the reproductive tract,including pro-inflammatory signals,which may play an important role during pregnancy.Vaginal lactobacilli are associated with positive pregnancy outcome,whereas bacterial vaginosis,a dysbiosis of the vaginal microbiome,is associated with an increased risk of adverse pregnancy outcomes including preterm birth.If the host response could be predicted based on the taxonomic composition of the vaginal microbiome,particularly early in pregnancy,then those predictions could potentially be used to personalize intervention methods to reduce preterm birth and other adverse events.In this proof of principle study,we apply multivariate strategies to analyze 16S rRNA-based taxonomic surveys in conjunction with targeted immuno-proteomic and lipidomic data from vaginal samples from 58 women enrolled in the Multi-Omic Microbiome Study-Pregnancy Initiative during early pregnancy.Relationships between the vaginal microbiome and the vaginal lipidome have not been previously reported.Results from this study reveal significant multiple pairwise associations between microbial taxa,specific eicosanoids and sphingomyelins,and cytokines.While the biologic significance of these associations is not yet known,these results support the utility of such multi-omic approaches as a means to predict the impact of the microbiome on the host.