RT Journal Article SR Electronic T1 Relationship between vaginal microbial dysbiosis, inflammation, and pregnancy outcomes in cervical cerclage JF Science Translational Medicine FD American Association for the Advancement of Science SP 350ra102 OP 350ra102 DO 10.1126/scitranslmed.aag1026 VO 8 IS 350 A1 Kindinger, Lindsay M. A1 MacIntyre, David A. A1 Lee, Yun S. A1 Marchesi, Julian R. A1 Smith, Ann A1 McDonald, Julie A. K. A1 Terzidou, Vasso A1 Cook, Joanna R. A1 Lees, Christoph A1 Israfil-Bayli, Fidan A1 Faiza, Yazmin A1 Toozs-Hobson, Philip A1 Slack, Mark A1 Cacciatore, Stefano A1 Holmes, Elaine A1 Nicholson, Jeremy K. A1 Teoh, T. G. A1 Bennett, Phillip R. YR 2016 UL http://stm.sciencemag.org/content/8/350/350ra102.abstract AB Cervical cerclage, a procedure that uses suture to reinforce the cervical opening, is frequently used to reduce the risk of preterm delivery in women with a history of previous preterm birth or short cervical length. Either monofilament or braided suture can be used for cerclage, but braided is more commonly selected because of its mechanical strength and easier application. A large clinical study by Kindinger et al. now shows that braided cerclage increases the risk of preterm birth and intrauterine death compared to monofilament suture. The authors also found that the braided suture is more conducive to bacterial colonization and increases the risk of vaginal dysbiosis and inflammation, helping to explain the clinical findings.Preterm birth, the leading cause of death in children under 5 years, may be caused by inflammation triggered by ascending vaginal infection. About 2 million cervical cerclages are performed annually to prevent preterm birth. The procedure is thought to provide structural support and maintain the endocervical mucus plug as a barrier to ascending infection. Two types of suture material are used for cerclage: monofilament or multifilament braided. Braided sutures are most frequently used, although no evidence exists to favor them over monofilament sutures. We assessed birth outcomes in a retrospective cohort of 678 women receiving cervical cerclage in five UK university hospitals and showed that braided cerclage was associated with increased intrauterine death (15% versus 5%; P = 0.0001) and preterm birth (28% versus 17%; P = 0.0006) compared to monofilament suture. To understand the potential underlying mechanism, we performed a prospective, longitudinal study of the vaginal microbiome in women at risk of preterm birth because of short cervical length (≤25 mm) who received braided (n = 25) or monofilament (n = 24) cerclage under comparable circumstances. Braided suture induced a persistent shift toward vaginal microbiome dysbiosis characterized by reduced Lactobacillus spp. and enrichment of pathobionts. Vaginal dysbiosis was associated with inflammatory cytokine and interstitial collagenase excretion into cervicovaginal fluid and premature cervical remodeling. Monofilament suture had comparatively minimal impact upon the vaginal microbiome and its interactions with the host. These data provide in vivo evidence that a dynamic shift of the human vaginal microbiome toward dysbiosis correlates with preterm birth.