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The vaginal Torquetenovirus titer varies with vaginal microbiota composition in pregnant women.

ABSTRACT: Torquetenovirus (TTV) is a nonpathogenic endogenous virus whose abundance varies with the extent of immune system activation. We determined if the TTV titer in the vagina of pregnant women was associated with vaginal microbiota composition and levels of compounds in vaginal secretions. Vaginal TTV and microbiota composition in 494 second trimester pregnant women were identified by gene amplification and analysis. Vaginal matrix metalloproteinases (MMPs), tissue inhibitors of MMP (TIMP) and lactic acid isomers were measured by ELISA. Dominance was defined as the relative abundance of a specific bacterium or species at >50% of the total number of bacteria identified. Clinical data were obtained by chart review. The median log10 TTV titer was lowest when Lactobacillus species other than L. iners were dominant (<1.0) as compared to when L. iners (4.1, p = 0.0001), bacteria other than lactobacilli (4.5, p = 0.0016) or no bacterium (4.7, p = 0.0009) dominated. The TTV titer was inversely proportional to L. crispatus abundance (p<0.0001) and directly proportional to levels of G. vaginalis (p = 0.0008) and L. iners (p = 0.0010). The TTV titer was proportional to TIMP-1, TIMP-2, MMP-8 and MMP-9 abundance (p≤0.0002) and inversely proportional to the level of D-lactic acid (p = 0.0024). We conclude that the association between variations in the TTV titer and the relative abundance of specific bacterial species and vaginal compounds indicates that local changes in immune status likely influence vaginal fluid composition.

SUBMITTER: Tozetto-Mendoza TR

PROVIDER: S-EPMC8775304 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Vaginal dysbiosis, such as bacterial vaginosis (BV) and aerobic vaginitis (AV), is an important cause of premature birth in pregnant women. However, there is very little research on vaginal microbial distribution in AV compared to that in BV. This study aimed to analyze the composition of the vaginal microbiota of pregnant women with AV using microbial community analysis and identify the causative organism using each criterion of the AV scoring system. Also, we compared the quantification of aerobic bacteria using quantitative polymerase chain reaction (qPCR) and their relative abundances (RA) using metagenomics. This prospective case-control study included 228 pregnant Korean women from our previous study. A wet mount test was conducted on 159 women to diagnose AV using the AV scoring system. Vaginal samples were analyzed using metagenomics, Gram staining for Nugent score determination, conventional culture, and qPCR for Staphylococcus spp., Streptococcus spp., and Enterobacteriaceae. The relative abundances (RAs) of eleven species showed significant differences among the three groups (Normal flora (NF), mild AV, and moderate AV). Three species including Lactobacillus crispatus were significantly lower in the AV groups than in the NF group, while eight species were higher in the AV groups, particularly moderate AV. The decrease in the RA of L. crispatus was common in three criteria of the AV scoring system (Lactobacillary, WBC, and background flora grades), while it did not show a significant difference among the three grade groups of the toxic leukocyte criterion. Also, the RAs of anaerobes, such as Gardnerella and Megasphaera, were higher in the AV groups, particularly moderate AV, while the RAs of aerobes were very low (RA < 0.01). Therefore, qPCR was performed for aerobes (Staphylococcus spp., Streptococcus spp., and Enterobacteriaceae); however, their quantification did not show a higher level in the AV groups when compared to that in the NF group. Therefore, AV might be affected by the RA of Lactobacillus spp. and the main anaerobes, such as Gardnerella spp. Activation of leukocytes under specific conditions might convert them to toxic leukocytes, despite high levels of L. crispatus. Thus, the pathogenesis of AV can be evaluated under such conditions.

Project description:The composition of the vaginal microbiota is heavily influenced by pregnancy and may factor into pregnancy complications, including spontaneous preterm birth. However, results among studies have been inconsistent due, in part, to variation in sample sizes and ethnicity. Thus, an association between the vaginal microbiota and preterm labor continues to be debated. Yet, before assessing associations between the composition of the vaginal microbiota and preterm labor, a robust and in-depth characterization of the vaginal microbiota throughout pregnancy in the specific study population under investigation is required. Here, we report a large longitudinal study (n = 474 women, 1,862 vaginal samples) of a predominantly African-American cohort-a population that experiences a relatively high rate of pregnancy complications-evaluating associations between individual identity, gestational age, and other maternal characteristics with the composition of the vaginal microbiota throughout gestation resulting in term delivery. The principal factors influencing the composition of the vaginal microbiota in pregnancy are individual identity and gestational age at sampling. Other factors are maternal age, parity, obesity, and self-reported Cannabis use. The general pattern across gestation is for the vaginal microbiota to remain or transition to a state of Lactobacillus dominance. This pattern can be modified by maternal parity and obesity. Regardless, network analyses reveal dynamic associations among specific bacterial taxa within the vaginal ecosystem, which shift throughout the course of pregnancy. This study provides a robust foundational understanding of the vaginal microbiota in pregnancy and sets the stage for further investigation of this microbiota in obstetrical disease. IMPORTANCE There is debate regarding links between the vaginal microbiota and pregnancy complications, especially spontaneous preterm birth. Inconsistencies in results among studies are likely due to differences in sample sizes and cohort ethnicity. Ethnicity is a complicating factor because, although all bacterial taxa commonly inhabiting the vagina are present among all ethnicities, the frequencies of these taxa vary among ethnicities. Therefore, an in-depth characterization of the vaginal microbiota throughout pregnancy in the specific study population under investigation is required prior to evaluating associations between the vaginal microbiota and obstetrical disease. This initial investigation is a large longitudinal study of the vaginal microbiota throughout gestation resulting in a term delivery in a predominantly African-American cohort, a population that experiences disproportionally negative maternal-fetal health outcomes. It establishes the magnitude of associations between maternal characteristics, such as age, parity, body mass index, and self-reported Cannabis use, on the vaginal microbiota in pregnancy.

Project description:BACKGROUND:This study was undertaken to characterize the vaginal microbiota throughout normal human pregnancy using sequence-based techniques. We compared the vaginal microbial composition of non-pregnant patients with a group of pregnant women who delivered at term. RESULTS:A retrospective case-control longitudinal study was designed and included non-pregnant women (n?=?32) and pregnant women who delivered at term (38 to 42 weeks) without complications (n?=?22). Serial samples of vaginal fluid were collected from both non-pregnant and pregnant patients. A 16S rRNA gene sequence-based survey was conducted using pyrosequencing to characterize the structure and stability of the vaginal microbiota. Linear mixed effects models and generalized estimating equations were used to identify the phylotypes whose relative abundance was different between the two study groups. The vaginal microbiota of normal pregnant women was different from that of non-pregnant women (higher abundance of Lactobacillus vaginalis, L. crispatus, L. gasseri and L. jensenii and lower abundance of 22 other phylotypes in pregnant women). Bacterial community state type (CST) IV-B or CST IV-A characterized by high relative abundance of species of genus Atopobium as well as the presence of Prevotella, Sneathia, Gardnerella, Ruminococcaceae, Parvimonas, Mobiluncus and other taxa previously shown to be associated with bacterial vaginosis were less frequent in normal pregnancy. The stability of the vaginal microbiota of pregnant women was higher than that of non-pregnant women; however, during normal pregnancy, bacterial communities shift almost exclusively from one CST dominated by Lactobacillus spp. to another CST dominated by Lactobacillus spp. CONCLUSION:We report the first longitudinal study of the vaginal microbiota in normal pregnancy. Differences in the composition and stability of the microbial community between pregnant and non-pregnant women were observed. Lactobacillus spp. were the predominant members of the microbial community in normal pregnancy. These results can serve as the basis to study the relationship between the vaginal microbiome and adverse pregnancy outcomes.

Project description:Abnormal vaginal microbiota (AVM), including bacterial vaginosis (BV), is caused by a microbiota imbalance. Nugent scoring is the gold standard for the laboratory diagnosis of BV; however, it is somewhat subjective to interpret, and challenging to distinguish bacteria. Hence, there is a need for improved technologies for the accurate diagnosis of AVM. To this end, next-generation sequencing (NGS) technology has been shown to yield comprehensive information on the pathophysiology of AVM. Hence, to evaluate the relationship between microbiota composition and the pathophysiology of AVM and its clinical significance, we characterized vaginal swab samples from 212 pregnant Korean women using both Nugent scoring and NGS analysis. Of these, the Nugent scoring identified 175 subjects (82.5%; 175/212) with normal flora (NF), 20 (9.4%; 20/212) with intermediate flora (IF), and 17 (8.0%; 17/212) with BV. NGS analysis followed by the characterization of vaginal microbiota composition, as represented by alpha and beta diversity, revealed the relative abundance of specific bacterial taxa at the genus and species level. Moreover, we identified all five predominant community state types (CSTs) along with three smaller CSTs. Analysis of the vaginal microbiota revealed the dominance of one or two Lactobacillus spp. in the NF group. Meanwhile, the IF and BV groups were dominated by the genera Gardnerella, Prevotella, and Atopobium. These two groups also showed higher alpha diversity than the NF group (p < 0.05). Principal coordinate analysis (PCoA) indicated that the NF group was significantly different from the AVM groups (p < 0.05), whereas no significant difference was observed between IF and BV groups (p = 0.25). Lastly, to investigate the characteristics of vaginal microbiota based on taxonomic composition, the IF and BV groups (AVM groups) were reclassified using the unweighted pair group method with arithmetic mean (UPGMA) clustering. Consequently, they were reclassified into BV1 (Lactobacillus iners-dominated), BV2-1 (Bifidobacterium breve-dominated), BV2-2 (Gardnerella vaginalis s1 or s2 and Atopobium vaginae-dominated), and BV3 [mixed population of G. vaginalis, L. iners, and other bacteria (p < 0.05)]. Collectively, these findings could serve to advance the current understanding regarding AVM pathophysiology.

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The vaginal Torquetenovirus titer varies with vaginal microbiota composition in pregnant women.

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