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.

项目摘要 随着全球抗逆转录病毒疗法（ART）的推广，越来越多的围产期获得性艾滋病的儿童 艾滋病毒（PHIV）存活到青春期及以后。接受抗逆转录病毒治疗的成年艾滋病毒感染者的风险增加 对于慢性年龄相关疾病，包括神经认知障碍，以及口腔疾病相比， 一般人口。这些疾病的早期前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抗逆转录病毒治疗相关的精神和口腔健康共病 可能是由重叠或不同的生物学和免疫学机制驱动的， 需要这些机制来支持干预措施，特别是在艾滋病毒感染者中。微生物群或衰老介导 这些过程已被证明直接导致艾滋病毒合并症。增加的发病率和流行率 我们小组和其他人在艾滋病毒感染者中观察到的牙齿病理似乎是由一种 病原微生物和寄生微生物的差异定植。新出现的证据表明， HIV感染改变了微生物群落，导致慢性低度炎症状态， 与年龄相关的条件与儿童和青少年PHIV。同时，观察到表观遗传年龄加速 与对照组相比，接受抗逆转录病毒治疗的成年艾滋病毒感染者中，的 该提案的目的是确定口腔微生物分类和功能特征，以及老化 与ALHIV患者的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NIH资助的约600名 生活在尼日利亚的围产期暴露（+/-PHIV）和未暴露（对照）HIV的儿童和青少年。在50 我们将分析ALHIV和50名性别和年龄匹配的未感染青少年（10 - 13岁） 唾液样本的宏基因组序列，以确定唾液分类和功能概况，并将使用 Illumina MethylationEPIC BeadChip阵列用于表征DNA甲基化和测量 血液样本中的表观遗传年龄加速标志物。在目标1中，我们将描述鸟枪代谢 唾液样本的序列和血液样本中表观遗传年龄加速的测量，以检查 （a）口腔微生物和功能概况与（B）表观遗传年龄加速之间的关联， 尼日利亚有和没有艾滋病毒的青少年的神经认知结果。在目标2中，我们将测试表观遗传是否 年龄加速与尼日利亚有和没有艾滋病毒的青少年的口腔健康结果有关。的 R01中提出的研究意义重大，因为它将产生关于微生物群-或衰老- 介导的机制导致ALHIV的神经认知障碍和口腔疾病。