Social Determinants and Vaginal Microbiome Effects on Preterm Birth in Hawaii

项目总结-社会决定因素和阴道微生物组对夏威夷早产的影响 早产（PTB）（在妊娠37周之前分娩新生儿）在土著人中发生率很高。 夏威夷人和太平洋岛民在夏威夷（NHPI），导致显着的长期新生儿发病率， 后代PTB的强生物标志物存在于母体阴道微生物组中。特定 厌氧物种丰度的特征、卷曲乳杆菌的消耗以及 乳酸杆菌导致炎症细胞因子和代谢物，理论上引发分子级联反应 导致早产具有卷曲乳杆菌优势的女性患PTB的风险降低75% 与阴道微生物群落主要为加德纳菌或其他厌氧菌的那些进行比较。然而，在这方面， 阴道微生物组组成也存在种族差异，目前尚不清楚这种高风险阴道微生物组是否存在种族差异。 微生物组特征预示着NHPI社区中PTB的类似风险。除了种族和民族差异， 健康的社会决定因素，如收入、营养、获得医疗保健或系统性种族主义的影响， 在微生物群落组成中发挥作用，并可能随后导致PTB风险。 该项目的最初目标是建立在2010年有PTB风险的女性的阴道微生物组概况。 夏威夷长期目标是创建一种使用阴道分子信号预测PTB的即时检测， 了解受阴道生态失调影响的炎症途径，可以通过靶向治疗进行调节 预防PTB。作为实现这一目标的基础步骤，我们的项目将解决以下具体目标： 1.）的人。比较低风险经产妇女中PTB风险妇女的阴道微生物组成。 假设：早产的妇女将有更高丰度的乳酸杆菌或厌氧物种 沿着炎症标记物和相关代谢物在妊娠早期。研究方法：妊娠 在妊娠中期（14-22周），有PTB风险的妇女和健康对照将收集阴道拭子样品。 将进行16 S测序，分配α和β多样性概况，并确定群落状态类型。 （CSTs）或指定的优势物种。从阴道拭子中，将测量炎性细胞因子水平 用多重ELISA;和用质谱法测量代谢物。这些指标将进行比较 在早产和未早产的女性中。2.）的情况。确定社会关系 健康和阴道微生物群的决定因素在妇女谁做和不经历PTB。假设： 社会逆境和压力增加，没有弹性（忍受困难的能力），导致饮食不良 质量，与阴道微生物生态失调和随后的PTB增加有关。研究方法： 参与者将完成一份调查汇编，其中包括与压力、焦虑、饮食和健康有关的问题。 摄入量、粮食不安全、种族主义和复原力。机器学习技术将用于识别 PTB风险模式简介，包括环境暴露和主要微生物物种。

PROJECT SUMMARY - Social Determinants and Vaginal Microbiome Effects on Preterm Birth in Hawaii Preterm Birth (PTB) (delivery of a neonate before 37 weeks gestation) occurs at high rates in Native Hawaiians and Pacific Islanders in Hawaii (NHPI), resulting in significant long term neonatal morbidity of their offspring. Strong biologic markers for PTB are present within the maternal vaginal microbiome. A particular signature of anaerobic species abundance, depletion of Lactobacillus crispatus, and predominance of Lactobacillus iners results in inflammatory cytokines and metabolites theorized to set off a molecular cascade leading to preterm labor. Women with Lactobacillus Crispatus predominance have a 75% lower risk of PTB compared those with vaginal microbial community primarily of Gardnerella or other anerobic species. However, ethnic variation also exists in vaginal microbiome composition, and it is unknown if this same high risk vaginal microbiome profile portends similar risk of PTB in NHPI communities. In addition to racial and ethnic variation, social determinants of health such as income, nutrition, access to healthcare, or effects of systemic racism also play a role in microbial community composition, and may subsequently contribute to PTB risk. The initial goal of this project is to establish vaginal microbiome profiles of women at risk for PTB in Hawaiʻi. The long-term goal is to create a point of care test to predict PTB using vaginal molecular signals, and understand inflammatory pathways affected by vaginal dysbiosis that could be modulated with targeted therapy to prevent PTB. As foundational steps toward this goal, our project will address the following Specific Aims: 1.) Compare vaginal microbial composition in women at risk of PTB among low-risk multiparous women. Hypothesis: Women who deliver preterm will have higher abundance of Lactobacillus iners or anerobic species along with inflammatory markers and associated metabolites in early pregnancy. Research Approach: Pregnant women at risk for PTB and healthy controls will collect vaginal swab samples during mid-gestation (14-22 weeks). 16S sequencing will be performed, alpha and beta diversity profiles assigned, and Community State Types (CSTs) or predominant species designated. From vaginal swabs, inflammatory cytokines levels will be measured with multi-plex ELISA; and metabolites measured with mass spectroscopy. These metrics will be compared among women who did and did not deliver preterm. 2.) Determine the association between social determinants of health and vaginal microbiota in women who do and do not experience PTB. Hypothesis: Increased social adversity and stress, unmitigated by resiliency (ability to endure hardship), leading to poor diet quality, are associated with increased vaginal microbial dysbiosis, and subsequent PTB. Research Approach: Participants will complete a compilation of surveys including questions pertaining to stress, anxiety, dietary intake, food insecurity, perceived racism and resiliency. Machine learning techniques will be used to identify a PTB risk pattern profile incorporating environmental exposures and predominant microbial species.