Relationship between vaginal microbial dysbiosis, inflammation, and pregnancy outcomes in cervical cerclage

被引:134
作者
Kindinger, Lindsay M. [1 ,2 ,3 ]
MacIntyre, David A. [1 ]
Lee, Yun S. [1 ]
Marchesi, Julian R. [4 ,5 ]
Smith, Ann [5 ]
McDonald, Julie A. K. [4 ]
Terzidou, Vasso [1 ,6 ]
Cook, Joanna R. [1 ]
Lees, Christoph [1 ,2 ,7 ]
Israfil-Bayli, Fidan [8 ]
Faiza, Yazmin [9 ]
Toozs-Hobson, Philip [8 ]
Slack, Mark [9 ]
Cacciatore, Stefano [1 ]
Holmes, Elaine [4 ,10 ]
Nicholson, Jeremy K. [4 ,10 ]
Teoh, T. G. [3 ]
Bennett, Phillip R. [1 ,2 ]
机构
[1] Imperial Coll London, Imperial Coll Parturit Res Grp, London W12 0NN, England
[2] Imperial Coll Healthcare Natl Hlth Serv NHS Trust, Queen Charlottes Hosp, London W12 0HS, England
[3] Imperial Coll Healthcare NHS Trust, St Marys Hosp, London W2 1NY, England
[4] Imperial Coll London, Ctr Digest & Gut Hlth, London W2 1NY, England
[5] Cardiff Univ, Sch Biosci, Cardiff CF10 3AX, S Glam, Wales
[6] Imperial Coll Healthcare NHS Trust, Chelsea & Westminster Hosp, London SW10 9NH, England
[7] Katholieke Univ Leuven, Dept Dev & Regenerat, B-3000 Leuven, Belgium
[8] Birmingham Womens Hosp NHS Fdn Trust, Birmingham B15 2TG, W Midlands, England
[9] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Urogynaecol Dept, Cambridge CB2 0QQ, England
[10] Imperial Coll London, Dept Surg & Canc, Div Computat Syst Med, London SW7 2AZ, England
基金
英国医学研究理事会;
关键词
BACTERIAL-VAGINOSIS; PRETERM DELIVERY; GARDNERELLA-VAGINALIS; POSTPARTUM PERIOD; BIOFILM FORMATION; SUTURE MATERIAL; RISK-FACTORS; WOMEN; BIRTH; LABOR;
D O I
10.1126/scitranslmed.aag1026
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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页数:12
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