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

项目总结/摘要 慢性艾滋病毒感染仍然是一个公共卫生挑战，全世界有近3800万人感染艾滋病毒。 艾滋病毒/艾滋病的尽管抗逆转录病毒治疗在抑制病毒复制方面取得了成功，但许多 挑战仍然存在，包括慢性炎症和合并症的加速发作。更好地理解 必须进一步减少合并症并改善这些现象的机制， 治疗艾滋病毒。微生物组由数万亿不同的微生物（细菌，真菌，病毒）组成， 多种证据强调了微生物组、粘膜免疫系统和 HIV相关炎症虽然肠道微生物组一直是密集研究的焦点，但 了解口腔微生物组在健康和疾病中的作用。在非艾滋病毒环境中， 与炎症相关的合并症如心血管疾病的风险增加有关。 最近的证据也强调了口腔和肠道微生物之间的联系， 在许多炎性疾病中已经观察到肠中耐氧“口腔”细菌的定殖， 包括艾滋病毒。在艾滋病毒背景下检查口腔微生物组的研究是有限的， 研究了口腔肠道细菌易位、生态失调发作和全身性 感染HIV。我们假设细菌从口腔移位到肠道有助于 慢性HIV感染中的生态失调的发展。此外，我们假设口腔微生物组 导致慢性HIV的局部和全身炎症，这种改变的粘膜环境可能 增加口腔感染易感性。使用纵向标本，新的唾液分析， 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 口腔微生物群对HIV感染者肠道生态失调和全身炎症的贡献; 2） 确定唾液伊加对关键口腔细菌的反应与局部和全身性 炎症;以及3）识别可能预测口腔性传播感染风险的特定口腔细菌 (STI)感染和未感染艾滋病毒的高危人群。这项工作将有助于更好地界定复杂的关系 口腔微生物组，炎症和HIV感染易感性之间的关系;发展的关键步骤 新的策略和唾液监测工具，以更好地治疗艾滋病毒和减少合并症。

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.