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 这项研究将研究与肠道相关的临床结果和免疫代谢后果 艾滋病毒感染的老年人的微生物组概况。肠道微生物组的不良偏移已关联 患有慢性非传染性疾病（尤其是心血管疾病[CVD]）和HIV感染。 肠道微生物组的组成也与健康衰老和发展的度量有关 衰老成年人的脆弱，肌肉减少症和认知能力下降。我们对肠道微生物组及其如何的理解 潜在的免疫和代谢途径导致CVD和老年综合症的多余负担 艾滋病毒的老年人不完整。从全球设置中尤其需要此数据 艾滋病毒疾病史，特有共同感染以及社会和经济环境塑造了微生物组 作品。使用先前收集的样品，该样品来自大型纵向队列研究的成年人 在巴西的HIV，这项研究将检查（1）与相关的微生物组组成和功能谱 CVD和老年综合征以及（2）与炎症途径相关的微生物组代谢产物 这有助于这些条件。利用纵向收集的丰富临床和社会数据 巴西的艾滋病毒和衰老研究（R01AG071439），我们将首先表征肠道微生物组的组成 所有参与者（n = 700）检查微生物组轮廓如何预测普遍存在的CVD和老年病 综合征，在考虑年龄等混杂因素之后（包括CD4细胞计数） Nadir），存在慢性共同感染和社会经济因素。在嵌套队列（n = 90名参与者）中， 我们将更具体地研究促炎性微生物组的存在是否预测 使用尖端的分子基因组方法，普遍的CVD和老年综合征。最后，探索 肠道营养不良和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HIV成年人的CVD和老年综合征相关的特定炎症途径的升高。 基于一项强大的国际协作研究，探讨了慢性共同感染如何影响衰老 这项补充研究在艾滋病毒成年人的成年人中的结果增加了重要的检查 共生微生物。补充研究将由关键研究共同评估者领导，并进一步丰富 整个半球的协作网络。