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 慢性艾滋病毒感染使公共卫生挑战率是一项公共卫生挑战，全世界有近3800万人与与之生活在一起。 艾滋病毒/艾滋病。 仍然存在挑战，包括慢性炎症和合并症的加速发作。 有助于这些现象的机制必须进一步进一步 艾滋病毒的治疗。 高度证据高于微生物组，粘膜免疫系统和 hile hile the的重点是某种焦点somesearch 关于口服微生物组在非HIV环境中的作用，口腔微生物组 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Hasso强调了口腔和肠道微生物组之间的联系，并增加了 在许多炎症疾病中观察到了肠道中的气化“口服” Bactteria的定植， 包括艾滋病毒的研究。 检查了口腔与肠道肠易位，营养不良的发作与全身性的关系 艾滋病毒中的炎症。 慢性艾滋病毒感染中的营养不良。 在慢性艾滋病毒中有助于局部和全身炎症，这种改变的粘膜环境可能 使用纵向标本来增加口服感染的敏感性。 流行病学临床结果我们将系统地解决我们的假设。 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； 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 （STI）在有和没有艾滋病毒的高危人中。 口服微生物组，炎症和艾滋病毒感染的感染; 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。