Cervicovaginal microbiota and local immune response modulate the risk of spontaneous preterm delivery

Cervicovaginal microbiota and local immune response modulate the risk of spontaneous preterm delivery
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DOI:
10.1038/s41467-019-09285-9
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发表时间:
2019-03-21
影响因子:
16.6
通讯作者:
Ravel, Jacques
Ravel, Jacques
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Elovitz, Michal A.;Gajer, Pawel;Ravel, Jacques

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未能预测和了解早产的原因,这是新生儿发病率和死亡率的主要原因,有效的干预和治疗措施有限。从2000名孕妇队列中,我们对107例表型良好的自然早产(SPTB)和432例足月分娩的孕妇进行了嵌套病例对照研究。使用创新的宫颈阴道微生物区系的贝叶斯模型,七种细菌分类群与sPTB风险的增加显著相关,在非裔美国女性中影响更大。然而,较高的阴道β-防御素-2水平降低了与宫颈阴道微生物区系相关的sPTB的风险,这与种族有关。令人惊讶的是,即使在乳杆菌中也是如此。宫颈阴道微生物区系占优势,低β-防御素-2与sPTB风险增加相关。这些发现为诊断准确识别怀孕早期有患肺结核风险的妇女提供了希望。治疗策略可以包括免疫调节剂和基于微生物组的疗法,以减轻这一重大的健康负担。
Failure to predict and understand the causes of preterm birth, the leading cause of neonatal morbidity and mortality, have limited effective interventions and therapeutics. From a cohort of 2000 pregnant women, we performed a nested case control study on 107 well-phenotyped cases of spontaneous preterm birth (sPTB) and 432 women delivering at term. Using innovative Bayesian modeling of cervicovaginal microbiota, seven bacterial taxa were significantly associated with increased risk of sPTB, with a stronger effect in African American women. However, higher vaginal levels of beta-defensin-2 lowered the risk of sPTB associated with cervicovaginal microbiota in an ethnicity-dependent manner. Surprisingly, even in Lactobacillus spp. dominated cervicovaginal microbiota, low beta-defensin-2 was associated with increased risk of sPTB. These findings hold promise for diagnostics to accurately identify women at risk for sPTB early in pregnancy. Therapeutic strategies could include immune modulators and microbiome-based therapeutics to reduce this significant health burden.