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      Increased richness and diversity of the vaginal microbiota and spontaneous preterm birth

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          Abstract

          Background

          The bacterial community present in the female lower genital tract plays an important role in maternal and neonatal health. Imbalances in this microbiota have been associated with negative reproductive outcomes, such as spontaneous preterm birth (sPTB), but the mechanisms underlying the association between a disturbed microbiota and sPTB remain poorly understood. An intrauterine infection ascending from the vagina is thought to be an important contributor to the onset of preterm labour. Our objective was to characterize the vaginal microbiota of pregnant women who had sPTB ( n = 46) and compare to those of pregnant women who delivered at term ( n = 170). Vaginal swabs were collected from women at 11–16 weeks of gestational age. Microbiota profiles were created by PCR amplification and pyrosequencing of the cpn60 universal target region.

          Results

          Profiles clustered into seven community state types: I ( Lactobacillus crispatus dominated), II ( Lactobacillus gasseri dominated), III ( Lactobacillus iners dominated), IVA ( Gardnerella vaginalis subgroup B or mix of species), IVC ( G. vaginalis subgroup A dominated), IVD ( G. vaginalis subgroup C dominated) and V ( Lactobacillus jensenii dominated). The microbiota of women who experienced preterm birth (< 37 weeks gestation) had higher richness and diversity and higher Mollicutes prevalence when compared to those of women who delivered at term. The two groups did not cluster according to CST, likely because CST assignment is driven in most cases by the dominance of one particular species, overwhelming the contributions of more rare taxa. In conclusion, we did not identify a specific microbial community structure that predicts sPTB, but differences in microbiota richness, diversity and Mollicutes prevalence were observed between groups.

          Conclusions

          Although a causal relationship remains to be determined, our results confirm previous reports of an association between Mollicutes and sPTB and further suggest that a more diverse microbiome may be important in the pathogenesis of some cases.

          Electronic supplementary material

          The online version of this article (10.1186/s40168-018-0502-8) contains supplementary material, which is available to authorized users.

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          Most cited references55

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            A Metagenomic Approach to Characterization of the Vaginal Microbiome Signature in Pregnancy

            While current major national research efforts (i.e., the NIH Human Microbiome Project) will enable comprehensive metagenomic characterization of the adult human microbiota, how and when these diverse microbial communities take up residence in the host and during reproductive life are unexplored at a population level. Because microbial abundance and diversity might differ in pregnancy, we sought to generate comparative metagenomic signatures across gestational age strata. DNA was isolated from the vagina (introitus, posterior fornix, midvagina) and the V5V3 region of bacterial 16S rRNA genes were sequenced (454FLX Titanium platform). Sixty-eight samples from 24 healthy gravidae (18 to 40 confirmed weeks) were compared with 301 non-pregnant controls (60 subjects). Generated sequence data were quality filtered, taxonomically binned, normalized, and organized by phylogeny and into operational taxonomic units (OTU); principal coordinates analysis (PCoA) of the resultant beta diversity measures were used for visualization and analysis in association with sample clinical metadata. Altogether, 1.4 gigabytes of data containing >2.5 million reads (averaging 6,837 sequences/sample of 493 nt in length) were generated for computational analyses. Although gravidae were not excluded by virtue of a posterior fornix pH >4.5 at the time of screening, unique vaginal microbiome signature encompassing several specific OTUs and higher-level clades was nevertheless observed and confirmed using a combination of phylogenetic, non-phylogenetic, supervised, and unsupervised approaches. Both overall diversity and richness were reduced in pregnancy, with dominance of Lactobacillus species (L. iners crispatus, jensenii and johnsonii, and the orders Lactobacillales (and Lactobacillaceae family), Clostridiales, Bacteroidales, and Actinomycetales. This intergroup comparison using rigorous standardized sampling protocols and analytical methodologies provides robust initial evidence that the vaginal microbial 16S rRNA gene catalogue uniquely differs in pregnancy, with variance of taxa across vaginal subsite and gestational age.
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              The vaginal microbiome during pregnancy and the postpartum period in a European population

              The composition and structure of the pregnancy vaginal microbiome may influence susceptibility to adverse pregnancy outcomes. Studies on the pregnant vaginal microbiome have largely been limited to Northern American populations. Using MiSeq sequencing of 16S rRNA gene amplicons, we characterised the vaginal microbiota of a mixed British cohort of women (n = 42) who experienced uncomplicated term delivery and who were sampled longitudinally throughout pregnancy (8–12, 20–22, 28–30 and 34–36 weeks gestation) and 6 weeks postpartum. We show that vaginal microbiome composition dramatically changes postpartum to become less Lactobacillus spp. dominant with increased alpha-diversity irrespective of the community structure during pregnancy and independent of ethnicity. While the pregnancy vaginal microbiome was characteristically dominated by Lactobacillus spp. and low alpha-diversity, unlike Northern American populations, a significant number of pregnant women this British population had a L. jensenii-dominated microbiome characterised by low alpha-diversity. L. jensenii was predominantly observed in women of Asian and Caucasian ethnicity whereas L. gasseri was absent in samples from Black women. This study reveals new insights into biogeographical and ethnic effects upon the pregnancy and postpartum vaginal microbiome and has important implications for future studies exploring relationships between the vaginal microbiome, host health and pregnancy outcomes.
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                Author and article information

                Contributors
                aline.freitas@usask.ca
                abocking@mtsinai.on.ca
                janet.hill@usask.ca
                deborah.money@ubc.ca
                Journal
                Microbiome
                Microbiome
                Microbiome
                BioMed Central (London )
                2049-2618
                28 June 2018
                28 June 2018
                2018
                : 6
                : 117
                Affiliations
                [1 ]ISNI 0000 0001 2154 235X, GRID grid.25152.31, Department of Veterinary Microbiology, , University of Saskatchewan, ; Saskatoon, SK S7N 5B4 Canada
                [2 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Departments of Obstetrics and Gynaecology and Physiology, , University of Toronto, ; Toronto, ON M5G 1L4 Canada
                [3 ]ISNI 0000 0004 0473 9881, GRID grid.416166.2, Lunenfeld-Tanenbaum Research Institute, ; M5T1X5, Toronto, ON Canada
                [4 ]ISNI 0000 0001 2288 9830, GRID grid.17091.3e, Department of Obstetrics and Gynaecology, , University of British Columbia, ; Vancouver, BC V6T 1Z4 Canada
                [5 ]ISNI 0000 0000 9878 6515, GRID grid.413264.6, Women’s Health Research Institute, , BC Women’s Hospital & Health Centre, ; Vancouver, BC V6H 3N1 Canada
                Article
                502
                10.1186/s40168-018-0502-8
                6022438
                29954448
                487502f8-a0c5-4717-aafa-43bcafa1fa46
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 19 October 2017
                : 18 May 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000024, Canadian Institutes of Health Research;
                Award ID: 108030
                Award ID: 108030
                Award ID: 108030
                Award ID: MOP-82799
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100008920, University of Saskatchewan;
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                microbiome,vagina,lactobacillus,cst,diversity,richness,mollicutes,preterm birth,pregnancy,infection

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