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

项目概要/摘要 背景当有害的社会环境（例如，贫穷和歧视）燃料 相互作用的生物和心理健康状况增加了艾滋病毒等疾病的风险。 精神健康状况不佳、物质使用和创伤的综合征与性风险和 妇女和性少数男子中的艾滋病毒血清转换（即，同性恋、双性恋和其他有性行为的男性 男人）。然而，需要对共同的生物途径进行更多的研究， Syndemics可能会影响免疫系统，扩大高优先人群感染艾滋病毒的风险。的 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降低有关。 能力，增加了感染艾滋病毒的风险。心理健康、物质使用和危险行为 分别与生态失调和炎症有关。然而，没有研究模拟这些因素 一起作为一个Syndemic，并探讨了直肠或宫颈阴道生态失调的Syndemic相关性， 与粘膜免疫力降低相关的阴道/直肠环境的特征。方法.这 F32将涉及两种方法：（1）进行一项子研究，将心理社会症状测量添加到一项 正在进行的R 01（5 R 01 AI 138718 -02; PI：Alcaide） 调查妇女细菌性阴道病的预测因素， 检查症状因素之间的关系（例如，精神健康、物质使用、创伤）和阴道 （2）利用最近完成的92例HIV-1感染者的研究中现有的16 S rRNA测序数据， 在南佛罗里达，性传播感染诊所招募了一名阴性的性少数男性， 综合症和直肠生态失调（艾滋病保健基金会; 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Syndemic过程如何扩大重点人群的艾滋病毒风险。培训计划。通过 实践培训，教学法，并与多学科导师团队（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， 在临床心理学和粘膜免疫学领域架起桥梁。这份F32奖学金申请将奠定 为K23提案奠定基础，以开发和测试针对Syndemic条件的生物行为干预措施 改善心理健康，解决微生物组的生态失调，并改善粘膜免疫功能 与高度优先人群中的艾滋病毒感染有关。影响。F32研究的结果和 培训计划是迈向独立研究项目的重要的第一步， 连接症状和粘膜免疫功能的机制，目的是减少 边缘化人口在艾滋病毒相关的健康方面的差距。

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.