Uncovering the Biological Link between Oral and Mental health in Adolescents Living with HIV (uBLOoM)

揭示感染艾滋病毒的青少年口腔和心理健康之间的生物联系 (uBLOoM)

• 批准号: 10670575
• 负责人: MODUPE COKER
• 金额: $ 23.27万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 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 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10670575
• 关键词: Acceleration; Adolescence; Adolescent; Adult; Age; Aging; Attention; Bacteria; Bioinformatics; Biological; Biological Markers; Biological Process; Blood specimen; Caring; Child; Chronic; Cognition; DNA Methylation; Data; Data Set; Dental; Dental Hygiene; Dental caries; Dentistry; Development; Disease; Epidemiology; Epigenetic Process; Funding; General Population; Gingiva; HIV; HIV Infections; HIV-infected adolescents; Health; Immunologics; Incidence; Inflammatory; Interdisciplinary Study; Intervention; Leptotrichia; Link; Measures; Mediating; Medicine; Mental Health; Metabolic; Metagenomics; Microbe; Microbial Taxonomy; Microbiology; Mouth Diseases; Neisseria; Neurocognition; Neurocognitive; Neurocognitive Deficit; Neurologic; Neuropsychology; Nigeria; Nigerian; Oral; Oral health; Outcome; Pathogenesis; Pathology; Pediatrics; Perinatal; Perinatal Exposure; Persons; Population; Prevalence; Prevention strategy; Process; Research; Risk; Role; Salivary; Sampling; Shapes; Shotguns; Statistical Models; Streptococcus mutans; Taxonomy; Testing; Therapeutic; United States National Institutes of Health; Variant; Work; Youth; age related; aged; antiretroviral therapy; bead chip; behavior influence; clinically relevant; cognitive testing; cohort; commensal microbes; comorbidity; comparison control; cost effective; disorder risk; epigenetic marker; executive function; high risk; insight; interdisciplinary approach; microbial; microbial community; microbiota; multidimensional data; oral condition; oral microbial community; pathogenic bacteria; pathogenic microbe; peer; predictive tools; programs; saliva sample; scale up; sex; social influence

PROJECT SUMMARY With the global scale-up of antiretroviral therapy (ART), increasing numbers of children with perinatally-acquired HIV (PHIV) are surviving into adolescence and beyond. Adults living with HIV on ART are at an increased risk for chronic age-related illnesses, including neurocognitive impairment, as well as oral disease compared to the general population. Early precursors of these disorders are also highly prevalent in children and adolescents living with HIV (ALHIV). Given that mental and oral health co-morbidities associated with HIV and lifelong ART could be driven by overlapping or distinct biological and immunological mechanisms, a better understanding of these mechanisms is needed to support interventions, particularly among ALHIV. Microbiota- or aging-mediated processes have been shown to contribute directly to HIV comorbidities. Increased incidence and prevalence of dental pathologies observed by our group and others among people living with HIV appears predicated by a differential colonization with pathogenic and commensal microbes. Emerging evidence suggests that controlled HIV infection alters microbial communities, contributing to a chronic low-grade inflammatory state that underlies age-associated conditions in children and youth with PHIV. In parallel, epigenetic age acceleration is observed in adults with HIV on ART when compared to controls and has been linked to neurocognitive deficits. The objective of this proposal is to identify oral microbial taxonomic and functional features, and aging markers associated with neurocognition and oral health in ALHIV. Our multidisciplinary research team is comprised of experts in HIV epidemiology, microbiology, dentistry, medicine, pediatrics, neuropsychology, bioinformatics and statistical modeling. We will leverage an established NIH-funded cohort of approximately 600 children and adolescents perinatally exposed (+/- PHIV) and unexposed (controls) to HIV living in Nigeria. In 50 ALHIV and 50 sex- and age-matched uninfected adolescents (aged 10-13), we will analyze shotgun metagenomic sequences of salivary samples to identify salivary taxonomic and functional profiles and will use the comprehensive Illumina MethylationEPIC BeadChip array to characterize DNA methylation and measure markers of epigenetic age acceleration in blood samples. In Aim 1, we will characterize shotgun metabolic sequences of salivary samples and measures of epigenetic age acceleration in blood samples to examine associations between (a) oral microbial and functional profiles and (b) epigenetic age acceleration with neurocognition outcomes in Nigerian adolescents with and without HIV. In Aim 2, we will test whether epigenetic age acceleration is associated with oral health outcomes in Nigerian adolescents with and without HIV. The research proposed in this R01 is significant because it will generate new insights into how microbiota- or aging- mediated mechanisms contribute to neurocognitive impairments and oral conditions in ALHIV.

项目总结 随着全球抗逆转录病毒治疗(ART)的扩大，越来越多的儿童患有围产期获得性疾病 艾滋病毒(PHIV)正在存活到青春期及以后。接受抗逆转录病毒治疗的成年人感染艾滋病毒的风险增加 对于与年龄相关的慢性疾病，包括神经认知障碍以及口腔疾病，与 普通人口。这些疾病的早期先兆在儿童和青少年中也非常普遍。 艾滋病毒携带者(ALHIV)鉴于与艾滋病毒和终身艺术相关的心理和口腔健康并存 可能是由重叠或不同的生物和免疫机制驱动的，更好地理解 需要这些机制来支持干预措施，特别是在ALHIV中。微生物区系或衰老调节 事实证明，这一过程直接导致了艾滋病毒的共病。增加的发病率和流行率 我们小组和其他人在艾滋病毒携带者中观察到的牙科病理似乎是由 病原微生物和共生微生物的不同定植。新出现的证据表明，受控的 HIV感染改变了微生物群落，导致了慢性低度炎症状态 艾滋病毒携带者儿童和青年的年龄相关性疾病。同时，观察到表观遗传年龄加速。 在成年艾滋病毒携带者中，接受抗逆转录病毒治疗的患者与对照组相比，与神经认知缺陷有关。这个 这项建议的目的是确定口腔微生物分类和功能特征，以及衰老 ALHIV患者与神经认知和口腔健康相关的标志物。我们的多学科研究团队是 由艾滋病毒流行病学、微生物学、牙科、医学、儿科、神经心理学、 生物信息学和统计建模。我们将利用由美国国立卫生研究院资助的约600人的现有队列 生活在尼日利亚的围产期接触艾滋病毒(+/-PHIV)和未接触艾滋病毒(对照)的儿童和青少年。在50年内 ALHIV和50名性别和年龄匹配的未感染青少年(10-13岁)，我们将分析猎枪 唾液样本的基因组序列，以确定唾液的分类和功能图谱，并将使用 用于DNA甲基化表征和检测的综合光甲基化EPIC珠片阵列 血液样本中表观遗传年龄加速的标志物。在目标1中，我们将描述鸟枪式新陈代谢 唾液样本序列和血液样本表观遗传加速措施的检测 (A)口腔微生物和功能谱与(B)表观遗传年龄加速之间的关系 感染和未感染艾滋病毒的尼日利亚青少年的神经认知结果。在目标2中，我们将测试表观遗传学 在尼日利亚感染和不感染艾滋病毒的青少年中，年龄加速与口腔健康结果有关。这个 本R01中提出的研究具有重要意义，因为它将对微生物区系-或衰老-产生新的见解 中介机制有助于ALHIV患者的神经认知障碍和口腔疾病。