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The role of the enteric microbiome in chronic HIV pathogenesis and cardiovascular disease in HIV-infected individuals

肠道微生物组在艾滋病毒感染者慢性艾滋病发病机制和心血管疾病中的作用

基本信息

批准号：
9271428
负责人：
David Benjamin Gootenberg
金额：
$ 4.68万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9271428
关键词：
Address Adenoviruses Affect Africa South of the Sahara African Archaea Atherosclerosis Bacteria Bile Acids Cardiovascular Diseases Cardiovascular Pathology Cardiovascular system Cell model Cells Cessation of life Chronic Clinical Coculture Techniques Collection Communities Data Data Set Development Diabetes Mellitus Disease Disease Outcome Enteral Epithelial Feces Foam Cells Functional disorder Goals HIV HIV Infections HIV Seropositivity Health High-Throughput Nucleotide Sequencing Human Immune In Vitro Individual Inflammation Inflammatory Inflammatory Response Intestines Kidney Lactobacillus Lead Lecithin Life Expectancy Link Lipids Longevity Macrophage Activation Measurement Measures Mediating Metabolic Metadata Methods Microbe Modeling Monitor Mus Obesity Organism Outcome Parasites Participant Pathogenesis Pathology Patients Permeability Physiological Platelet Activation Population Production Quality of life Reporting Research Personnel Role Serum Serum Markers Symbiosis System Therapeutic Intervention Thrombosis Training Transplantation Ursidae Family Viral Virus Work antiretroviral therapy career cohort computerized tools cytokine dietary constituent effective therapy gut microbiome immune activation improved in vivo in vivo Model interest intimal medial thickening macrophage microbial microbial community microbiome microbiota mortality mouse model novel pathogenic bacteria trimethyloxamine

项目摘要

Project Summary/Abstract Even with antiretroviral therapy, Human Immunodeficiency Virus (HIV)-infected individuals still have a greater mortality than uninfected individuals, mostly due to death from inflammation-related non-communicable diseases (NCD), such as cardiovascular disease (CVD) and kidney dysfunction. The drivers of this chronic immune activation and associated CVD remain largely unknown. Recent studies have shown that there might be significant HIV-associated disruptions in the gut microbial community, which is essential to human health and is involved in many metabolic and immune interactions. Our preliminary data from Sub-Saharan African populations, which bear a great burden of HIV and associated CVD, suggest that there are clear shifts in this microbial community and that these correspond to increased measures of systemic inflammation. Independent of HIV, changes in the gut microbial community have been shown to produce inflammatory metabolites that cause macrophage and platelet activation, thrombosis, and arterial plaque formation. We propose to study HIV-associated gut microbial changes in Sub-Saharan African populations and measure systemic immune activation and cardiovascular outcomes associated with these changes. We will then use in vitro and in vivo models to investigate the causative relationship between HIV-associated gut microbial community changes and CVD. To accomplish this goal, we will expose gut cell models to HIV-associated microbes of interest and measure the inflammatory response to these organisms. We will also transplant mouse models of atherosclerosis with stool microbial communities and then quantify the development of CVD induced by these communities. It is our hope that this work will identify mechanisms by which the gut microbial community might contribute to CVD pathogenesis in chronic HIV and provide opportunities for therapeutic interventions to extend lifespan and improve quality of life for HIV-infected individuals.

项目总结/文摘