Bacterial and Cytokine Mixtures Predict the Length of Gestation and are Associated with miRNA Expression in the Cervix

Abstract

Aim: Bacterial vaginosis may lead to preterm birth through epigenetic programming of the inflammatory response, specifically via miRNA expression. Methods: We quantified bacterial 16S rRNA, cytokine mRNA and 800 miRNA from cervical swabs obtained from 80 women at 16–19 weeks’ gestation. We generated bacterial and cytokine indices using weighted quantile sum regression and examined associations with miRNA and gestational age at delivery. Results & discussion: Each decile of the bacterial and cytokine indices was associated with shorter gestations (p < 0.005). The bacterial index was associated with miR-494, 371a, 4286, 185, 320e, 888 and 23a (p < 0.05). miR-494 remained significant after false discovery rate correction (q < 0.1). The cytokine index was associated with 27 miRNAs (p < 0.05; q < 0.01). Conclusion: Future investigation into the role of bacterial vaginosis- and inflammation-associated miRNA and preterm birth is warranted.

Keywords::

• bacterial vaginosis
• cervix
• cytokines
• miRNA
• preterm birth

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/epi-2016-0095

Acknowledgements

The authors thank E Reuckert at NanoString Technologies for his assistance with the miRNA/RNA expression profiling and analyses. They thank the ABC Medical Center in Mexico City for providing facilities during data collection.

Financial and competing interests disclosures

This work was supported in part by Pilot Project funding from the HSPH-NIEHS Center for Environmental Health (ES000002) and NIH/NIEHS: K23ES022242, P30ES23515, R01ES013744, R01ES014930, R01ES020268, R01ES021357, the Klarman Scholars Program at Beth Israel Deaconess Medical Center, the Harvard Catalyst D-MaPS Program and the National Institute of Public Health/Ministry of Health of Mexico. The funding organizations had no role in study design, data collection, analysis or interpretation, or preparation of the manuscript for publication. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The International Review Boards of the participating institutions approved this study: Brigham and Women’s Hospital #2006-P-001416 and P001792, Icahn School of Medicine at Mount Sinai human subjects management #12-00751 and Instituto Nacional de Salud Publica project #560. Written informed consent was obtained from women participating in the PROGRESS study.

Additional information

Funding

This work was supported in part by Pilot Project funding from the HSPH-NIEHS Center for Environmental Health (ES000002) and NIH/NIEHS: K23ES022242, P30ES23515, R01ES013744, R01ES014930, R01ES020268, R01ES021357, the Klarman Scholars Program at Beth Israel Deaconess Medical Center, the Harvard Catalyst D-MaPS Program and the National Institute of Public Health/Ministry of Health of Mexico. The funding organizations had no role in study design, data collection, analysis or interpretation, or preparation of the manuscript for publication. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.