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

项目摘要/摘要 背景资料。当有害的社会环境(例如贫穷和歧视)助长时，就会出现联结性 生物和心理健康状况相互作用，增加了艾滋病毒等疾病的风险。 精神健康不良、药物使用和创伤的症状与性风险和 妇女和性少数民族男子(即男同性恋、双性恋和其他有性行为的男子)的艾滋病毒血清转换 和男人)。然而，有必要对共同的生物途径进行额外的研究，通过这些途径 综合症可能会影响免疫系统，从而放大高优先级人群感染艾滋病毒的风险。这个 HIV感染最有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力下降有关 能力，增加了感染艾滋病毒的风险。精神健康、药物使用和危险行为 表现出与生物失调和炎症的不同关系。然而，还没有研究对这些因素进行建模。 共同探讨了直肠或宫颈阴道失调和 阴道/直肠环境的特点与粘膜免疫力下降有关。方法：研究方法。这 F32将涉及两种方法：(1)进行一项子研究，将心理社会综合指标添加到 正在进行的R01(5R01AI138718-02；PI：阿尔凯德) 调查女性细菌性阴道病的预测因素 检查共同因素(例如，精神健康、药物使用、创伤)和阴道之间的关系 以及(2)利用最近完成的一项对92名艾滋病毒感染者的研究的现有16S rRNA测序数据 南佛罗里达州性行为阴性的少数族裔男性在性传播感染诊所招募，以检查两者之间的关系 合并症和直肠生物失调(艾滋病医疗基金会；PI：CARICO)。通过这两项研究， 将获得关于非生物微生物群作为共同途径的相关性的基本知识 解释共同程序如何能够放大优先人群中的艾滋病毒风险。培训计划。穿过 实践培训、教学以及与多学科指导团队(Carrico、Klatt、Alcaide、 和Safren)，申请者将接受艾滋病毒预防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奖学金申请将为 K23提案的基础工作，以开发和测试针对突发性疾病的生物行为干预措施 改善心理健康，解决微生物群失调问题，改善粘膜免疫功能 与高优先人群中的艾滋病毒感染有关。这意味着什么。这项F32研究的发现和 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 联结合并症和粘膜免疫功能的机制，目的是减少 被边缘化人口与艾滋病毒相关的健康差距。

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.