The Microbiome of Pregnant African American Women with Group B Streptococcus Colonization and the Influence of Prenatal Antibiotics

项目摘要/摘要 B群链球菌(GBS)感染是#年感染性新生儿发病率和死亡率的主要原因。 我们。母亲GBS定植是新生儿GBS感染的最强预测因子。非裔美国人(AA) 母亲和婴儿感染GBS的可能性是白人的两倍。目前有 没有有效的方法来防止母体GBS定植。目前为预防母婴GBS所做的努力 在分娩期间传播中心周围给筛查的母亲在产中使用抗生素 定植阳性，这减少了早发性新生儿GBS败血症的病例数量；但这 这种方法不能预防GBS相关的并发症，这些并发症发生在分娩前，也不能预防迟发性败血症。 此外，AA和他们的白人之间的GBS脓毒症的差异仍然没有解释， 没有特点，尽管实施了产期抗生素，但仍持续存在，强调需要 进一步了解形成GBS殖民的因素。初步数据显示，接触抗生素 产前，这在再生障碍性贫血妇女中更常见，可能会增加GBS定植的风险。《降临》 微生物组的元基因组测序为解决抗生素这一重要微生物提供了希望 临床难题。到目前为止，还没有研究系统地检查围产期抗生素暴露和/或 妊娠期间与母体GBS定植有关的微生物组的动态。为了更好地 了解GBS的差异，确定风险和保护因素，本研究将检查口腔、肠道和 再生障碍性贫血孕妇孕期阴道微生物群的研究这项嵌套的病例对照研究将有助于 提高对再障孕妇GBS定植相关产前危险因素的认识 妇女通过评估16S rRNA和医疗记录数据来实现以下目标：1)评估 GBS阳性与阴性孕妇妊娠早期和晚期的阴道、肠道和口腔微生物群 筛选培养。2)确定产前接触抗生素是否易患GBS或预防GBS 与GBS定殖化相关的定殖化和/或微生物群模式。 这项研究的结果有可能改变实践，改善孕妇的抗生素管理。 人口。该奖项支持的K01项目和辅导培训是为Wright博士设计的 在量化围产期暴露和微生物组分析管道方面建立专门知识。与她相结合 现有的表观遗传学和护理专业知识，额外的培训建立了多学科的专业知识 基金会支持独立的、翻译的研究计划，专注于开发个性化 以及机械针对性的干预措施，以改善整个生命周期的健康结果。

Project Summary/Abstract Group B streptococcal (GBS) infection is the leading cause of infectious neonatal morbidity and mortality in the US. Maternal GBS colonization is the strongest predictor for neonatal GBS infection. African American (AA) mothers and infants are twice as likely to be affected by GBS than their white counterparts. There are currently no effective methods to prevent maternal GBS colonization. Current efforts to prevent maternal-infant GBS transmission during labor center around the administration of intrapartum antibiotics to mothers who screen positive for colonization, which has reduced the number of cases of early onset neonatal GBS sepsis; but this approach does not prevent GBS associated complications that occur prior to labor nor late onset sepsis. Furthermore, the disparity of GBS sepsis between AAs and their white counterparts remains unexplained, uncharacterized, and persistent despite the implementation of intrapartum antibiotics, underscoring the need to further understand factors that shape GBS colonization. Preliminary data suggests that exposure to antibiotics prenatally, which is more common among AA women, may increase the risk for GBS colonization. The advent of metagenomic sequencing of the microbiome offers promise for solving this important microbe-antibiotic clinical puzzle. To date, no studies have systematically examined perinatal antibiotic exposure and/or the dynamics of the microbiome related to maternal GBS colonization throughout pregnancy. In order to better understand the GBS disparity, identify risk and protective factors, this study will examine the oral, gut, and vaginal microbiome of AA pregnant women throughout pregnancy. This nested case-control study will serve to advance the understanding of prenatal risk factors associated with GBS colonization among AA pregnant women by evaluating 16S rRNA and medical record data to accomplish the following Aims: 1) Evaluate the vaginal, gut, and oral microbiome in early and later pregnancy among women with GBS positive vs. negative screening culture. 2) Determine whether prenatal antibiotic exposures predispose to, or protect against, GBS colonization and/or microbiome patterns associated with GBS colonization. Results from this study have the potential to change practice and improve antibiotic stewardship in pregnant populations. The K01 project and mentored training supported by this award were designed for Dr. Wright to establish expertise in quantifying perinatal exposures and microbiome analytic pipelines. Combined with her existing expertise in epigenetics and nursing, the additional training establishes multi-omic expertise as the foundation to sustain an independent, translational program of research focused on developing personalized and mechanistically-targeted interventions to improve health outcomes across the lifespan.