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Tracking the Microbiome Origin of Inflammation from Mouth to Placenta in Preeclampsia
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23-175HS-1
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Tracking the Microbiome Origin of Inflammation from Mouth to Placenta in Preeclampsia
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Dr. Yanjiao Zhou
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AIMS Preeclampsia (PE) is defined by high blood pressure and proteinuria in pregnancy. It affects approximately 2-8% of the overall pregnant population and 17-25% of pregnant women with chronic hypertension. It is a leading cause of maternal death. Pathogenesis of PE involves excessive immune response, maternal endothelial dysfunction and abnormal placenta development. However, the initial factors responsible for the development of PE are unknown. Oral microbiota, comprising over 700 different bacterial species, has been linked not only to local periodontal diseases, but also systemic disorders. It has been speculated that oral microbiota can disseminate to placenta through blood circulation, heightening immune response and increasing risk of PE. Indeed, our recent work that tracked the oral and placental microbiome simultaneously in patients showed that the relative abundances of Haemophilus, Veillonella and Fusobacterium in subgingival plaque were significantly higher in patients with PE than matched controls without PE. We also rigorously identified the presence of these oral-like bacteria in placenta of PE patients, in contrast to controls. The preliminary data was based on samples collected at the delivery; thus, it is unclear whether the oral microbiome alteration is an acute process at PE onset or as a result of gradual alteration over the pregnancy term. It is also unclear when placental microbiome seeding occurs. A longitudinal profiling of the oral microbiome during pregnancy is critical to capture the overall dynamics of the microbiome in PE development, and provide novel insight into oral microbiome in pathogenesis of PE. Dysregulation of Th17/Tregs cells is a major contributor of pathogenesis of PE. Recent research showed that oral microbiome alteration in periodontal diseases can trigger Th17 cells to mediate oral mucosal immunopathology in an IL-6 dependent manner. Our preliminary data showed oral-like microbiota in placenta of PE patients were associated with elevated IL-6 in blood, raising a possibility that oral microbiome alteration may contribute to exaggerated immune response in PE through upregulation of IL-6 and Th17 cells. We hypothesize that an altered microbiome-immune interaction during pregnancy contributes to development of preeclampsia. We propose a prospective longitudinal study to determine dynamics of oral microbiome and immune response over different gestation and their association with PE. Aim 1. Determine the dynamics of the oral microbiome throughout pregnancy and their association with PE. We will prospectively enroll 100 patients with chronic hypertension or who meet criteria for being at risk of PE at UConn and Hartford Hospital. We will collect subgingival samples at each trimester and at PE onset, along with placenta at delivery. We will compare the oral microbiome of each trimester and at PE onset between patients who develop and who do not develop PE, and identify PE associated oral microbiome after controlling confounding factors. Placenta microbiome will be correlated with PE and oral microbiome. Aim 2. Determine the dynamics of immune response and immune-microbiome interactions throughout pregnancy. Blood will be collected at the same time as Aim1 in the study participants for immune assay. PBMC will be used to determine immune cell populations by flow cytometry focusing on Th17 and Tregs cells. Serum will be used to measure multiple panels of cytokines and chemokines by high- throughput Luminex assay. We will determine the association of oral microbiome at each trimester and placental microbiome with immune measures after controlling clinical confounding factors. Impact. The study holds promises to gain insight into the pathogenies of PE from a novel oral microbiome-immune interaction perspective, and lay ground work for future to develop non-invasive microbiome markers to predict PE. We will apply a R01 to extend the study to multi-centers to cross-validate the microbiome and immune findings. We also plan to collect and bank stool and vaginal samples from the study to create multiple lines of research on the microbiome and PE at Departments of Medicine and OB/GYN in future.
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Obstetrics and Gynecology
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Check with study contact
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Makayla Murphy. Telephone: 860-679-3331. Email: makmurphy@uchc.edu or Kristen Annis. Telephone: 860-679-3812. Email: annis@uchc.edu
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Enrolling/recruiting. For current recruitment status, please check with study contact.
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