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The vaginal microbiome and preterm birth.

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PubMed ID: 31142849

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Fettweis JM, Serrano MG, Brooks JP, Edwards DJ, Girerd PH, Parikh HI, Huang B, Arodz TJ, Edupuganti L, Glascock AL, Xu J, Jimenez NR, Vivadelli SC, Fong SS, Sheth NU, Jean S, Lee V, Bokhari YA, Lara AM, Mistry SD, Duckworth RA, Bradley SP, Koparde VN, Orenda XV, Milton SH, Rozycki SK, Matveyev AV, Wright ML, Huzurbazar SV, Jackson EM, Smirnova E, Korlach J, Tsai YC, Dickinson MR, Brooks JL, Drake JI, Chaffin DO, Sexton AL, Gravett MG, Rubens CE, Wijesooriya NR, Hendricks-Muñoz KD, Jefferson KK, Strauss JF, Buck GA

Nat Med. Jun 2019. doi: 10.1038/s41591-019-0450-2

COMMENT: This work has been developed within the integrative Human Microbiome Project (iHMP) to study the relationships between vaginal microbiome and preterm birth searching for microbiome biomarkers useful for evaluating the risk of Preterm birth (PTB). Considering that Preterm birth is the second most common cause of neonatal death, this work is important and provides some new findings to advance in the prevention of PTB.

It is known that a healthy female reproductive tract is dominated by Lactobacillus and recent reports have suggested that the composition of the vaginal microbiome could have impact on Preterm birth risk. Recent studies reported that Lactobacillus crispatus correlated with a lower risk of preterm birth. It is also confirmed in this study

RESULTS

In the present study, we report a community resource that includes samples collected longitudinally during 1,572 pregnancies of women from diverse ancestries, and omics data generated from samples collected from 597 pregnancies in a collaborative effort under the umbrella of the National Institutes of Health’s integrative Human Microbiome Project (iHMP)41. Furthermore, we provided an analysis of the longitudinal, comprehensive, multi-omic profiling of vaginal samples from 45 women who experienced spontaneous PTB and 90 case-matched controls, in a cohort of women of predominantly African ancestry. In an initial analysis of this dataset, which represents one of the largest and most comprehensive studies of the vaginal microbiome to date, we identified vaginal microbial signatures in women who went on to experience PTB.

As a proof of concept, we developed a model for identifying the most discriminative taxa for PTB using 16S rRNA data from samples collected at 24 weeks of gestation or earlier. Model construction involved selecting taxa that are differentially represented in the cohorts as assessed using the Mann–Whitney U-test, and assigning weights to these taxa using L1-regularized logistic regression. The resulting model incorporates four taxa: Sneathia amnii, BVAB1, Prevotella cluster 2 and TM7-H1, which are all positively correlated with PTB

CONCLUSIONS:

In the present study, we developed a proof-of-concept model that suggests the presence of BVAB1, Prevotella cluster 2, S. amnii and TM7-H1 early in pregnancy may be useful for prediction of risk for PTB, particularly in high-risk populations

... bacterial taxa generally associated with dysbiosis are highly correlated with expression of proinflammatory cytokines, which may play a role in the induction of labor. Labor is associated with proinflammatory cytokine expression, and premature labor can be induced by host inflammatory responses.

Taken together, our data suggest that, coupled with other clinical and possibly genetic factors, microbiome-associated taxonomic, metabolic and immunologic biomarkers may be useful in defining the risk of PTB, and that this risk might be assessed early in pregnancy

DATA AVAILABILITY:

Open-access data including raw 16S rRNA sequences, cytokine data and limited metadata are available at the HMP DACC (https://portal.hmpdacc.org). Controlled-access data including raw MGS data, raw MTS data and metadata for all subjects analyzed in this study are available at National Center for Biotechnology Information’s controlled-access dbGaP (study no. 20280; accession ID phs001523.v1.p1) and the SRA under BioProject IDs PRJNA326441, PRJNA326442 and PRJNA326441. The genomes of TM7-H1 (CP026537) and BVAB1 (PQVO000000) have been submitted to GenBank. Access to additional fields can be requested through the RAMS Registry (https://ramsregistry.vcu.edu). Additional project information is available at the project’s website (http://vmc.vcu.edu/momspi).

Contributor

Raquel Tobes