Longitudinal Study of HIV and Aging in Brazil

巴西艾滋病毒与老龄化的纵向研究

• 批准号: 10846040
• 负责人: Jessica L Castilho
• 金额: $ 43.56万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10846040
• 关键词: 16S ribosomal RNA sequencing; Accounting; Acquired Immunodeficiency Syndrome; Adult; Affect; Age; Age Years; Aging; Amino Acids; Atherosclerosis; Biological Markers; Blood; Brazil; CD4 Lymphocyte Count; Cardiometabolic Disease; Cardiovascular Diseases; Chronic; Chronic Disease; Cities; Clinical; Communities; Country; Data; Dementia; Development; Disease; Economics; Elderly; Environment; Fatty Acids; Feces; Funding; Future; Genomic approach; Geriatric Assessment; HIV; HIV Infections; Human; Immune; Immune system; Immunologics; Immunology; Impaired cognition; Income; Individual; Inflammatory; International; Intervention; Investigation; Kynurenine; Lead; Link; Lipids; Longitudinal Studies; Longitudinal cohort study; Measurement; Measures; Medical; Metabolic; Metabolic Pathway; Metabolism; Molecular; Morbidity - disease rate; Outcome; Participant; Pathway interactions; Pharmaceutical Preparations; Physical Function; Plasma; Predisposition; Prospective Studies; Quality of life; Recording of previous events; Research; Research Personnel; Risk; Role; Sampling; Serology; Shapes; Site; Socioeconomic Factors; Standardization; Structure; Swab; Syndrome; Testing; Toxoplasmosis; Tryptophan; Tuberculosis; United States National Institutes of Health; Urine; Virus Diseases; Volatile Fatty Acids; antiretroviral therapy; clinical phenotype; co-infection; cohort; commensal microbes; experience; frailty; gut dysbiosis; gut microbiome; gut microbiota; healthy aging; hexanoic acid; improved; interest; metagenomic sequencing; microbial; microbiome; microbiome alteration; microbiome composition; nutrition; participant enrollment; sarcopenia; social; systemic inflammatory response; tool; ultrasound

PROJECT SUMMARY This study will investigate the clinical outcomes and immunometabolism consequences associated with gut microbiome profiles in older people living with HIV. Adverse shifts in the gut microbiome have been associated with chronic non-communicable diseases (particularly cardiovascular disease [CVD]) and HIV infection. Composition of the gut microbiome is also associated with measures of healthy aging and development of frailty, sarcopenia, and cognitive decline in aging adults. Our understanding of how the gut microbiome and its potential immune and metabolic pathways contribute to the excess burden of CVD and geriatric syndromes in older adults with HIV is incomplete. This data is particularly needed from global settings where differences in HIV disease history, endemic co-infections, and social and economic settings shape the microbiome composition. Using previously collected samples from a large, longitudinal cohort study of aging adults with HIV in Brazil, this study will examine (1) the microbiome composition and functional profiles associated with CVD and geriatric syndromes and (2) the microbiome metabolites associated with inflammatory pathways which contribute to those conditions. Leveraging the rich clinical and social data collected in the Longitudinal Study of HIV and Aging in Brazil (R01AG071439), we will first characterize the gut microbiome composition of all participants (n=700) to examine how the microbiome profiles predict prevalent CVD and geriatric syndromes, after accounting for confounders such as age, HIV disease biomarkers (including CD4 cell count nadir), presence of chronic co-infections, and socioeconomic factors. In a nested cohort (n=90 participants), we will examine more specifically whether the presence of pro-inflammatory microbiome species predicts prevalent CVD and geriatric syndromes using cutting-edge, molecular genomic approaches. Finally, to explore potential immunometabolism mechanisms of gut dysbiosis and CVD and geriatric syndromes, we will measure whether alterations in plasma microbiome metabolites (amino acids and short chain fatty acids) predict elevations in specific inflammatory pathways associated with CVD and geriatric syndromes in adults with HIV. Building upon a robust, international collaborative study exploring how chronic co-infections affect aging outcomes in adults with HIV, this supplemental study adds the important examination into the role of commensal microbes. The supplemental study will be led by key study co-investigators and further enrich the collaborative network across the hemisphere.

项目摘要 本研究将调查与肠道疾病相关的临床结局和免疫代谢后果。 老年艾滋病毒感染者的微生物组概况。肠道微生物组的不利变化与 慢性非传染性疾病（特别是心血管疾病[CVD]）和艾滋病毒感染。 肠道微生物组的组成也与健康老龄化的措施和发展有关。 老年人的虚弱、肌肉减少和认知能力下降。我们对肠道微生物组及其 潜在的免疫和代谢途径导致CVD和老年综合征的过度负担， 老年人感染艾滋病毒是不完整的。全球环境尤其需要这种数据， HIV病史、地方性合并感染以及社会和经济环境塑造了微生物组 混合物.使用先前从一项大型纵向队列研究中收集的样本， 在巴西的艾滋病毒，这项研究将检查（1）微生物组组成和功能概况相关的 CVD和老年综合征以及（2）与炎症途径相关的微生物组代谢物 导致了这些情况。利用纵向研究中收集的丰富临床和社会数据， 巴西艾滋病毒和老龄化研究（R01AG071439），我们将首先描述 所有参与者（n=700），以检查微生物组特征如何预测普遍的CVD和老年人 综合征，在考虑混杂因素，如年龄，HIV疾病生物标志物（包括CD4细胞计数 最低点）、慢性合并感染的存在以及社会经济因素。在嵌套队列中（n=90名参与者）， 我们将更具体地研究促炎微生物组物种的存在是否预示着 流行的心血管疾病和老年综合征使用尖端的，分子基因组方法。最后，为了探索 肠道生态失调和CVD和老年综合征的潜在免疫代谢机制，我们将测量 血浆微生物组代谢物（氨基酸和短链脂肪酸）的改变是否预测 与成人HIV感染者CVD和老年综合征相关的特定炎症途径升高。 建立在一项强有力的国际合作研究基础上，探索慢性合并感染如何影响衰老 这项补充研究增加了对艾滋病毒感染者的作用的重要检查， 浮游微生物补充研究将由关键研究合作研究者领导，并进一步丰富 在整个半球的合作网络。