Role of the oral microbiome in driving local and systemic inflammation in HIV

口腔微生物组在驱动艾滋病毒局部和全身炎症中的作用

• 批准号: 10762264
• 负责人: Jennifer Fulcher
• 金额: $ 76.16万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10762264
• 关键词: Acceleration; Address; Age; Antibodies; Automobile Driving; Bacteria; Bacterial Translocation; Binding; Cardiovascular Diseases; Chlamydia trachomatis; Chronic; Clinical; Complex; Data; Development; Disease; Disease Progression; Environment; Fc Receptor; Functional disorder; HIV; HIV Infections; HIV-1; HIV/AIDS; Health; Human papilloma virus infection; Immune; Immune Sera; Immunoglobulin A; Immunologic Markers; Infection; Inflammation; Inflammatory; Link; Literature; Machine Learning; Measures; Microbe; Monitor; Mucosal Immune System; Mucosal Immunity; Mucositis; Mucous Membrane; Myeloid Cells; Neisseria gonorrhoeae; Neurocognitive; Oral; Oral Characters; Oral Examination; Oral cavity; Oral mucous membrane structure; Outcome; Participant; Pathogenesis; Periodontal Diseases; Persons; Pharyngeal structure; Polymers; Populations at Risk; Predisposition; Process; Public Health; Research; Risk; Role; Saliva; Salivary immunoglobulin A; Sexually Transmitted Diseases; Shotguns; Single Nucleotide Polymorphism; Site; Specimen; Technology; Testing; Validation; Viral; Viremia; Virus Replication; Work; antiretroviral therapy; clinical epidemiology; co-infection; cohort; comorbidity; cytokine; dysbiosis; gut bacteria; gut dysbiosis; gut inflammation; gut microbes; gut microbiome; immune activation; improved; in vitro Assay; infection risk; inflammatory marker; interest; longitudinal analysis; metagenomic sequencing; microbial; microbiome; microbiome composition; microbiome signature; migration; monomer; mucosal site; novel; novel strategies; oral bacteria; oral infection; oral microbial community; oral microbiome; polymeric IgA; response; risk prediction; saliva analysis; success; systemic inflammatory response; time use; tool

PROJECT SUMMARY / ABSTRACT Chronic HIV infection remains a public health challenge with nearly 38 million people worldwide living with HIV/AIDS. Despite the success of antiretroviral therapy in suppressing ongoing viral replication, numerous challenges remain including chronic inflammation and accelerated onset of comorbidities. Better understanding of the mechanisms contributing to these phenomena is imperative to further reduce comorbidities and improve treatment of HIV. The microbiome is comprised of trillions of diverse microbes (bacterial, fungal, viral), and multiple lines of evidence highlight the connections between the microbiome, mucosal immune system, and HIV-related inflammation. While the intestinal microbiome has been the focus of intense research, less is known about the role of the oral microbiome in health and disease. In non-HIV settings, the oral microbiome has been associated with increased risk of inflammation-related comorbidities such as cardiovascular disease. Recent evidence has also highlighted the connection between the oral and gut microbiomes, and increased colonization of aerotolerant “oral” bacteria in the gut has been observed in many inflammatory diseases, including HIV. Studies examining the oral microbiome in the setting of HIV are limited, and none have examined the relationships between oral to gut bacteria translocation, onset of dysbiosis, and systemic inflammation in HIV. We hypothesize that bacterial translocation from the mouth to the gut contributes to the development of dysbiosis in chronic HIV infection. Further, we hypothesize that the oral microbiome contributes to local and systemic inflammation in chronic HIV, and this altered mucosal environment may increase susceptibility for oral infections. Using longitudinal specimens, novel saliva analyses, and epidemiologic clinical outcomes we will systematically address our hypotheses. We propose to: 1) determine the contribution of oral microbiota to gut dysbiosis and systemic inflammation in persons living with HIV; 2) define the relationship between salivary IgA responses to key oral bacteria and local and systemic inflammation; and 3) identify specific oral bacteria that may predict risk of oral sexually transmitted infections (STI) in at-risk persons with and without HIV. This work will help better define the complex relationships between the oral microbiome, inflammation, and infection susceptibility in HIV; a critical step for developing novel strategies and saliva-based monitoring tools to better treat HIV and reduce comorbidities.

项目摘要 /摘要 慢性艾滋病毒感染仍然是一个公共卫生挑战，全球近3800万人与 艾滋病毒/艾滋病。尽管抗逆转录病毒疗法在抑制持续的病毒复制方面取得了成功，但许多 仍然存在挑战，包括慢性炎症和合并症的加速发作。更好的理解 促成这些现象的机制必须进一步降低合并症并改善 艾滋病毒的治疗。微生物组由数万亿微生物（细菌，真菌，病毒）和 多种证据突出了微生物组，粘膜免疫系统和 HIV相关的炎症。虽然肠道微生物组一直是激烈研究的重点，但较少的IS 关于口腔微生物组在健康和疾病中的作用已知。在非HIV设置中，口服微生物组 与炎症相关的合并症（如心血管疾病）的风险增加有关。 最近的证据还强调了口腔和肠道微生物组之间的联系，并增加了 在许多炎症性疾病中观察到了肠道中气化剂“口服”细菌的定植， 包括艾滋病毒。研究HIV中检查口腔微生物组的研究有限，没有 检查了口服与肠道细菌易位发作和全身性的关系 艾滋病毒的炎症。我们假设细菌从口腔转移到肠道有助于 慢性HIV感染中营养不良的发展。此外，我们假设口服微生物组 为慢性艾滋病毒的局部和全身感染做出了贡献，这种改变的粘膜环境可能 对口腔感染的敏感性增加。使用纵向规格，新颖的唾液分析和 流行病学临床结果我们将系统地解决我们的假设。我们建议：1）确定 口服微生物群对HIV患者的肠道营养不良和全身性炎症的贡献； 2） 定义唾液IgA对关键口腔细菌的响应与局部和全身性的关系 炎; 3）确定可能预测口腔性传播感染风险的特定口服细菌 （STI）在有和没有艾滋病毒的高危人中。这项工作将有助于更好地定义复杂的关系 在HIV中的口腔微生物组，感染和感染敏感性之间；发展的关键步骤 新颖的策略和基于唾液的监测工具，以更好地治疗艾滋病毒并减少合并症。