Vaginal Microbiome and Metabolites in Preterm Birth

早产中的阴道微生物组和代谢物

• 批准号: 10673751
• 负责人: Anna Maya Powell
• 金额: $ 19.82万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-10 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10673751
• 关键词: Acetates; Affect; African; African American; Age; Anaerobic Bacteria; Bacteria; Bacterial Counts; Bacterial Vaginosis; Bioinformatics; Biological; Butyrates; Career Mobility; Clinical; Clinical Trials Design; Cohort Studies; Communities; Data; Data Analyses; Discipline of obstetrics; Disparity; Environment; Exclusion; Financial cost; Foundations; Genital; Genitalia; Goals; Gynecology; HIV; HIV Infections; HIV Seronegativity; HIV Seropositivity; HIV risk; Health Care Costs; Human; Inflammation; Inflammation Mediators; Inflammatory; Institution; Interdisciplinary Study; Interleukin-1 beta; Interleukin-6; Intervention; Lactic acid; Lactobacillus; Lactoferrin; Learning; Liquid substance; Measures; Mediating; Mentors; Metagenomics; Mucositis; Output; Pathway interactions; Patient Recruitments; Physicians; Population; Positioning Attribute; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Program Development; Propionates; Research; Research Design; Research Personnel; Resources; Risk; Role; Sampling; Scientist; Structure; Succinates; Techniques; Term Birth; Time; Training; Translating; Universities; Vagina; Viral Load result; Virus Shedding; Vision; Volatile Fatty Acids; Woman; Work; adverse pregnancy outcome; antileukoprotease; antimicrobial peptide; beta diversity; beta-Defensins; career development; cervicovaginal; chemokine; cohort; cytokine; design; dysbiosis; experience; experimental study; health care disparity; improved; indexing; inflammatory milieu; medical schools; metabolomics; microbiome; microbiome research; perinatal HIV; pregnant; preventive intervention; professor; rRNA Genes; reproductive; skills; transmission process; vaginal fluid; vaginal microbiome; vaginal microbiota; vaginal mucosa

PROJECT SUMMARY/ABSTRACT This proposal presents a five year research career development program focused on the study of vaginal microbiome contributions to preterm birth among women with HIV to expand the breadth and depth of understanding of vaginal dysbiosis in preterm birth (PTB). The candidate is currently an Assistant Professor of Gynecology and Obstetrics at Johns Hopkins University School of Medicine. The outlined proposal builds on the candidate’s previous research and clinical experience in pregnancy outcomes among women with HIV and integrates two new domains of expertise of her mentors, Drs. Irina Burd and Khalil Ghanem at Johns Hopkins: inflammatory pathways leading to PTB with vaginal microbiome research. The proposed experiments and didactic work will position the candidate with a unique set of cross disciplinary skills that will enable her to transition to independence as a physician scientist with expertise in cohort study design and microbiome bioinformatics. Bacterial vaginosis (BV), an alteration in the vaginal microbiome, nearly doubles the risk of preterm birth, delivery prior to 37 weeks, and affects one third of women of reproductive age. In the US, women with HIV experience a two-fold increased risk of PTB compared to women without HIV. Women with HIV who have a Lactobacilus-deficient/ anaerobe-dominant vaginal microbiota have increased vaginal inflammation, higher genital HIV viral load and increased HIV viral shedding. The lacking data in US-based pregnant women with HIV risk perpetuating significant healthcare disparities. It is unknown whether the underlying mechanism between HIV infection and PTB is driven by vaginal dysbiosis. The foundation of this proposal is based on prior data documenting vaginal dysbiosis as a potential driver for altered inflammatory pathways and adverse pregnancy outcomes, particularly among African American women. Women with HIV and vaginal dysbiosis have increased risk for genital mucosa inflammation and viral shedding. The role of vaginal dysbiosis in pregnancy among women with HIV has not been explored to date, nor have the effects of ART on the vaginal microbiome in pregnancy. Specifically, this proposal aims to: 1) compare the structure (relative and absolute abundance) and composition (diversity) of the vaginal microbiota of pregnant women with HIV who experience PTB versus term birth, 2) determine the extent to which vaginal microbiota function, measured by median difference in metabolites (short chain fatty acids), correlates with PTB, and 3) measure and compare cervico- vaginal concentrations of soluble inflammatory mediators (antimicrobial peptides and pro-inflammatory cytokines) in PTB. The scientific objective of this proposal is to begin to define the strength of the association between vaginal microbiota, markers of mucosal inflammation and PTB among women with HIV and generate hypotheses that inform the direction and design of subsequent studies focused on potential interventions.

项目总结/文摘

项目成果

Experience and Outcomes of Breastfed Infants of Women Living With HIV in the United States: Findings From a Single-Center Breastfeeding Support Initiative.

美国艾滋病毒感染者母乳喂养婴儿的经验和结果：单中心母乳喂养支持计划的调查结果。

• DOI: 10.1093/jpids/piab116
• 发表时间: 2022
• 期刊: Journal of the Pediatric Infectious Diseases Society
• 影响因子: 3.2
• 作者: Yusuf,HasiyaE;Knott-Grasso,MaryAnn;Anderson,Jean;Livingston,Alison;Rosenblum,Nadine;Sturdivant,Heather;Byrnes,KristenC;Powell,Anna;Sheffield,JeanneS;Enns,Justine;Persaud,Deborah;Golden,WilliamChristopher;Agwu,AllisonL
• 通讯作者: Agwu,AllisonL

Structural Racism and Adverse Pregnancy Outcomes Through the Lens of the Maternal Microbiome.

• DOI: 10.1097/aog.0000000000005345
• 发表时间: 2023-10-01
• 期刊: Obstetrics and gynecology
• 影响因子: 7.2

Data on Safety of Intravaginal Boric Acid Use in Pregnant and Nonpregnant Women: A Narrative Review.

• DOI: 10.1097/olq.0000000000001562
• 发表时间: 2021-12-01
• 期刊: SEXUALLY TRANSMITTED DISEASES
• 影响因子: 3.1
• 作者: Mittelstaedt, Rachel;Kretz, Alyssa;Levine, Michael;Handa, Victoria L.;Ghanem, Khalil G.;Sobel, Jack D.;Powell, Anna;Tuddenham, Susan
• 通讯作者: Tuddenham, Susan