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.

项目概要/摘要背景。当有害的社会环境（例如贫困和歧视）加剧时，就会发生综合症相互作用的生物和心理健康状况会增加艾滋病毒等疾病的风险。精神健康状况不佳、药物滥用和创伤等流行病已表明与性风险和性行为有关。女性和性少数男性（即同性恋、双性恋和其他有性行为的男性）之间的艾滋病毒血清转化与男人）。然而，需要对常见的生物学途径进行更多研究流行病可能会影响免疫系统，从而增加高优先人群感染艾滋病毒的风险。这 HIV 感染最可能的途径是通过直肠或宫颈阴道粘膜。生态失调（非最佳微生物组组成）和局部炎症与粘膜免疫功能下降有关能力，增加感染艾滋病毒的风险。心理健康、物质使用和危险行为显示出与菌群失调和炎症的独立关系。然而，没有研究对这些因素进行建模作为一个综合症一起探讨了直肠或宫颈阴道菌群失调的综合症相关性与粘膜免疫力下降相关的阴道/直肠环境特征。方法。这 F32 将涉及两种方法：(1) 进行一项子研究，将心理社会流行病措施添加到正在进行中的 R01（5R01AI138718-02；PI：Alcaide）研究女性细菌性阴道病的预测因素检查流行病因素（例如心理健康、药物滥用、创伤）和阴道炎之间的关系 (2) 利用最近完成的一项针对 92 名 HIV 患者的研究中的现有 16S rRNA 测序数据南佛罗里达州的性传播感染诊所招募了一些消极的性少数男性，以检查两者之间的关系流行性疾病和直肠生态失调（艾滋病医疗基金会；PI：Carrico）。通过这两项研究，将获得关于生态失调微生物组作为共同途径的相关性的基本知识解释流行病过程如何放大重点人群的艾滋病毒风险。培训计划。通过实践培训、教学以及与多学科指导团队（Carrico、Klatt、Alcaide、和 Safren），申请人将获得艾滋病毒预防中的心理神经免疫学培训，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弥合临床心理学和粘膜免疫学领域。此 F32 奖学金申请将奠定为 K23 提案制定和测试针对流行病的生物行为干预措施奠定基础改善心理健康，解决微生物组失调，并改善粘膜免疫功能与高优先人群中艾滋病毒感染相关。影响。 F32 研究的结果和培训计划是迈向以生物学为重点的独立研究计划的重要第一步连接流行病状况和粘膜免疫功能的机制，目的是减少边缘化人群经历的与艾滋病毒相关的健康差异。