Syndemics, the microbiome, and mucosal inflammation involved in HIV acquisition

与 HIV 感染相关的综合症、微生物组和粘膜炎症

基本信息

批准号：
10553118
负责人：
Emily Mellissa Cherenack
金额：
$ 7.11万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10553118
关键词：
16S ribosomal RNA sequencing AIDS prevention Acquired Immunodeficiency Syndrome Address Alcohol abuse Antibiotic Therapy Bacteria Bacterial Vaginosis Bioinformatics Biological Biological Process Bisexual Characteristics Clinic Clinical Clinical Psychology Communities Data Data Collection Development Discrimination Environment Epidemic Exposure to Fellowship Florida Foundations Gays HIV HIV Infections HIV Seronegativity HIV Seropositivity HIV risk Health Health Psychology Healthcare Immune Immune system Immunologics Immunology Inflammation Innate Immune Response Interdisciplinary Study Intervention Knowledge Link Measurement Measures Mental Depression Mental Health Mentors Mentorship Methods Modeling Mucosal Immune Responses Mucosal Immunity Mucositis Mucous Membrane Music Outcome Pathway interactions Population Poverty Process Psychoneuroimmunology Rectum Recurrence Reproductive Tract Infections Research Research Training Ribosomal RNA Risk Risk Behaviors Route Shotgun Sequencing Social Environment Stress Structure Testing Training Translational Research Translations Trauma Vagina Viral Woman bacterial community base biobehavior career career development cervicovaginal chemokine cytokine disorder risk dysbiosis experience gender-based violence health disparity immune function improved indexing marginalized population meetings men who have sex with men microbial microbiome microbiome composition mucosal site multidisciplinary novel programs psychologic psychosocial recruit rectal rectal microbiome rectal microbiota sexual minority men skills stimulant use substance use syndemic theories translational scientist transmission process vaginal microbiome vaginal mucosa

项目摘要

Project Summary/Abstract Background. A Syndemic occurs when harmful social contexts (e.g., poverty and discrimination) fuel interacting biological and psychological health conditions that increase risk for diseases such as HIV. Syndemics of poor mental health, substance use, and trauma have shown relationships with sexual risk and HIV seroconversion among women and sexual minority men (i.e., gay, bisexual, and other men who have sex with men). However, there is a need for additional research on common biological pathways through which Syndemics may impact the immune system to amplify risk of HIV acquisition in high priority populations. The most likely route of HIV infection is through the rectal or cervicovaginal mucosa. Dysbiosis (non-optimal microbiome composition) and local inflammation are associated with decreased mucosal immunological capabilities, increasing the risk of HIV acquisition. Mental health, substance use, and risk behaviors have shown separate relationships to dysbiosis and inflammation. However, no research has modeled these factors together as a Syndemic and explored the Syndemic correlates of rectal or cervicovaginal dysbiosis and characteristics of the vaginal/rectal environments associated with decreased mucosal immunity. Methods. This F32 will involve two approaches: (1) conduct a sub-study that will add psychosocial Syndemic measures to an ongoing R01 (5R01AI138718-02; PI: Alcaide) investigating predictors of bacterial vaginosis among women to examine the relationships among Syndemic factors (e.g., mental health, substance use, trauma) and vaginal dysbiosis and (2) leverage existing 16S rRNA sequencing data from a recently completed study of 92 HIV- negative sexual minority men in South Florida recruited in STI clinics to examine the relationship between Syndemic conditions and rectal dysbiosis (AIDS Healthcare Foundation; PI: Carrico). Through both studies, essential knowledge will be gained on the relevance of a dysbiotic microbiome as a common pathway explaining how Syndemic processes could amplify HIV risk in priority populations. Training Plan. Through hands-on training, didactics, and meetings with a multidisciplinary mentorship team (Carrico, Klatt, Alcaide, and Safren), the applicant will gain training on psychoneuroimmunology in HIV prevention, with a focus on the microbiome and mucosal immunology, and obtain exposure to sequencing-based bioinformatics analysis to bridge the fields of clinical psychology and mucosal immunology. This F32 fellowship application will lay the groundwork for a K23 proposal to develop and test bio-behavioral interventions targeting Syndemic conditions to improve mental health, address dysbiosis of the microbiome, and improve mucosal immune functioning relevant to HIV acquisition in high priority populations. Implications. Findings from this F32 research and training plan represent an important first step towards an independent research program focusing on biological mechanisms connecting Syndemic conditions and mucosal immune functioning, with the aim of decreasing HIV-related health disparities experienced by marginalized populations.

项目摘要/摘要背景。当有害的社会环境（例如贫困和歧视）燃料时，会发生辛迪克相互作用的生物学和心理健康状况增加了艾滋病毒等疾病的风险。精神健康，药物使用和创伤不良的联合系统已经显示出与性风险和性风险的关系妇女和性少数族裔男性（即同性恋，双性恋和其他性爱的男性）中的艾滋病毒血清转化与男人）。但是，需要对通用生物学途径进行更多研究联合学可能会影响免疫系统，以扩大高优先级人群中艾滋病毒的风险。这 HIV感染的途径最有可能通过直肠或宫颈阴道粘膜。营养不良（非最佳选择微生物组组成）和局部炎症与粘膜免疫学降低有关能力，增加艾滋病毒收购风险。心理健康，药物使用和风险行为具有显示了与营养不良和炎症的单独关系。但是，没有研究对这些因素进行建模一起作为联合性，并探讨直肠或宫颈阴道性营养不良的联合性相关性阴道/直肠环境的特征与粘膜免疫降低有关。方法。这 F32将涉及两种方法：（1）进行一个子研究，将在正在进行的R01（5R01AI138718-02; pi：alcaide）调查女性细菌性阴道病的预测因子检查联合因素（例如心理健康，药物使用，创伤）和阴道之间的关系营养不良和（2）从最近完成的92个HIV-的研究中利用现有的16S rRNA测序数据南佛罗里达州的负面性少数民族男性在STI诊所招募，以检查联合状况和直肠失调（AIDS Healthcare Foundation; PI：Carrico）。通过两项研究，基本知识将获得不植物微生物组作为通用途径的相关性解释联合过程如何在优先人群中扩大HIV风险。培训计划。通过动手培训，教学法和与多学科指导团队的会议（Carrico，Klatt，Alcaide，和Safren），申请人将获得有关预防艾滋病毒的心理肌免疫学培训，重点是微生物组和粘膜免疫学，并获得基于测序的生物信息学分析的暴露桥梁临床心理学和粘膜免疫学领域。该F32奖学金申请将奠定 K23提案的基础工作，以开发和测试针对辛迪血理条件的生物行为干预措施为了改善心理健康，请解决微生物组的营养不良，并改善粘膜免疫功能与高优先级人群中的艾滋病毒获取有关。含义。这项F32研究的结果以及培训计划代表着朝着关注生物学的独立研究计划迈出的重要第一步连接联合条件和粘膜免疫功能的机制，目的是减少边缘化人群经历的与HIV相关的健康差异。