title: Relationship between vaginal microbial dysbiosis, inflammation, and pregnancy outcomes in cervical cerclage.
abstract: 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.
authors.affiliation: Imperial College Parturition Research Group, Division of the Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0NN, UK. Queen Charlotte's Hospital, Imperial College Healthcare National Health Service (NHS) Trust, London W12 0HS, UK. St. Mary's Hospital, Imperial College Healthcare NHS Trust, London W2 1NY, UK.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Kindinger
authors.affiliation: Imperial College Parturition Research Group, Division of the Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0NN, UK. d.macintyre@imperial.ac.uk p.bennett@imperial.ac.uk.
authors.forename: David A
authors.initials: DA
authors.lastname: MacIntyre
authors.affiliation: Imperial College Parturition Research Group, Division of the Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0NN, UK.
authors.forename: Yun S
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Centre for Digestive and Gut Health, Imperial College London, London W2 1NY, UK. School of Biosciences, Cardiff University, Cardiff CF103AX, UK.
authors.forename: Julian R
authors.initials: JR
authors.lastname: Marchesi
authors.affiliation: School of Biosciences, Cardiff University, Cardiff CF103AX, UK.
authors.forename: Ann
authors.initials: A
authors.lastname: Smith
authors.affiliation: Centre for Digestive and Gut Health, Imperial College London, London W2 1NY, UK.
authors.forename: Julie A K
authors.initials: JA
authors.lastname: McDonald
authors.affiliation: Imperial College Parturition Research Group, Division of the Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0NN, UK. Chelsea and Westminster Hospital, Imperial College Healthcare NHS Trust, London SW10 9NH, UK.
authors.forename: Vasso
authors.initials: V
authors.lastname: Terzidou
authors.affiliation: Imperial College Parturition Research Group, Division of the Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0NN, UK.
authors.forename: Joanna R
authors.initials: JR
authors.lastname: Cook
authors.affiliation: Imperial College Parturition Research Group, Division of the Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0NN, UK. Queen Charlotte's Hospital, Imperial College Healthcare National Health Service (NHS) Trust, London W12 0HS, UK. Department of Development and Regeneration, Katholieke Universiteit Leuven, Leuven 3000, Belgium.
authors.forename: Christoph
authors.initials: C
authors.lastname: Lees
authors.affiliation: Birmingham Women's Hospital NHS Foundation Trust, Edgbaston, Birmingham B15 2TG, UK.
authors.forename: Fidan
authors.initials: F
authors.lastname: Israfil-Bayli
authors.affiliation: Urogynaecology Department, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
authors.forename: Yazmin
authors.initials: Y
authors.lastname: Faiza
authors.affiliation: Birmingham Women's Hospital NHS Foundation Trust, Edgbaston, Birmingham B15 2TG, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Toozs-Hobson
authors.affiliation: Urogynaecology Department, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Slack
authors.affiliation: Imperial College Parturition Research Group, Division of the Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0NN, UK.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cacciatore
authors.affiliation: Centre for Digestive and Gut Health, Imperial College London, London W2 1NY, UK. Division of Computational Systems Medicine, Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.affiliation: Centre for Digestive and Gut Health, Imperial College London, London W2 1NY, UK. Division of Computational Systems Medicine, Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK.
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.affiliation: St. Mary's Hospital, Imperial College Healthcare NHS Trust, London W2 1NY, UK.
authors.forename: T G
authors.initials: TG
authors.lastname: Teoh
authors.affiliation: Imperial College Parturition Research Group, Division of the Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0NN, UK. Queen Charlotte's Hospital, Imperial College Healthcare National Health Service (NHS) Trust, London W12 0HS, UK. d.macintyre@imperial.ac.uk p.bennett@imperial.ac.uk.
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Bennett
mesh_terms: D000328:Adult; D023802:Cerclage, Cervical / Q000009:adverse effects*; D016207:Cytokines / Q000378:metabolism; D064806:Dysbiosis / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D012189:Retrospective Studies; D014621:Vagina / Q000382:microbiology
chemical_list: D016207:Cytokines