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 随着抗逆转录病毒疗法（ART）的全球量表，围产期获得的儿童人数越来越多 艾滋病毒（PHIV）生存到青春期及以后。患有艾滋病毒艾滋病毒艺术的成年人的风险增加 与长期与年龄相关的疾病（包括神经认知障碍）以及与口腔疾病相比 一般人口。这些疾病的早期前体在儿童和青少年中也很普遍 与艾滋病毒（ALHIV）同住。鉴于与艾滋病毒和终身艺术相关的心理和口腔健康合并症 可以通过重叠或独特的生物学和免疫学机制来驱动，对 需要这些机制来支持干预措施，尤其是在ALHIV中。微生物群或衰老介导的 已显示过程直接有助于HIV合并症。增加的发生率和流行 我们的小组和其他艾滋病毒感染者观察到的牙科病理似乎是由 与致病性和共生微生物的差异定殖。新兴证据表明受控 艾滋病毒感染改变了微生物群落，导致了慢性低级炎症状态的依据 PHIV儿童和青少年与年龄相关的状况。同时，观察到表观遗传年龄的加速度 与对照组相比，在艾滋病毒艾滋病毒的成年人中，与神经认知缺陷有关。这 该建议的目的是确定口腔微生物分类学和功能特征，以及衰老 与ALHIV的神经认知和口腔健康相关的标记。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，神经心理学专家组成， 生物信息学和统计建模。我们将利用大约600的NIH资助的既定队伍 儿童和青少年周围暴露（+/- pHIV）和未暴露（对照组）居住在尼日利亚的艾滋病毒。在50中 ALHIV和50个性别和年龄匹配的未感染青少年（10-13岁），我们将分析shot弹枪 唾液样品的宏基因组序列，以识别唾液分类学和功能谱，并将使用 综合的Illumina甲基化甲基甲虫阵列以表征DNA甲基化并测量 血液样本中表观遗传年龄加速的标记。在AIM 1中，我们将描述shot弹枪代谢 血液样本中唾液样本的序列和表观遗传年龄加速的测量 （a）口腔微生物和功能谱之间的关联以及（b）表观遗传年龄加速与与 有和没有艾滋病毒的尼日利亚青少年的神经认知结果。在AIM 2中，我们将测试是否表观遗传 年龄加速与尼日利亚青少年有或没有艾滋病毒的口腔健康结果有关。这 在此R01中提出的研究很重要，因为它将对微生物群或衰老的方式产生新的见解。 介导的机制有助于ALHIV的神经认知障碍和口服状况。