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:9753338
- 负责人:
- 金额:$ 5万
- 依托单位:
- 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:
- 关键词:16S ribosomal RNA sequencingAddressAdenovirusesAffectAfrica South of the SaharaAfricanArchaeaAtherosclerosisBacteriaBile AcidsCardiovascular DiseasesCardiovascular PathologyCardiovascular systemCell modelCellsCessation of lifeChronicClinicalCoculture TechniquesCollectionCommunitiesDataData SetDevelopmentDiabetes MellitusDiseaseDisease OutcomeEnteralEpithelialFecesFoam CellsGoalsHIVHIV InfectionsHIV SeropositivityHealthHigh-Throughput Nucleotide SequencingHumanImmuneIn VitroIndividualInflammationInflammatoryInflammatory ResponseIntestinesKidneyLactobacillusLeadLecithinLife ExpectancyLinkLipidsLongevityMacrophage ActivationMeasurementMeasuresMediatingMetabolicMetadataMethodsMicrobeModelingMonitorMusObesityOrganismOutcomeParasitesParticipantPathogenesisPathologyPatientsPermeabilityPhysiologicalPlatelet ActivationPopulationProductionQuality of lifeReportingResearch PersonnelRoleSerumSerum MarkersSystemTherapeutic InterventionThrombosisTrainingTransplantationUrsidae FamilyViralVirusWorkantiretroviral therapycareercarotid intima-media thicknesscohortcomputerized toolscytokinedietary constituenteffective therapygut microbiomegut microbiotaimmune activationimprovedin vivoin vivo Modelinterestkidney dysfunctionmacrophagemicrobialmicrobial communitymicrobiomemicrobiotamortalitymouse modelnovelpathogenic bacteriatransplant modeltrimethyloxamine
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/摘要
即使有抗逆转录病毒治疗,人类免疫缺陷病毒(HIV)感染者仍有较大的
死亡率高于未感染者,主要是由于炎症相关的非传染性疾病
疾病(NCD),例如心血管疾病(CVD)和肾功能障碍。这种慢性病的驱动因素
免疫激活和相关CVD仍然是未知的。最近的研究表明,
肠道微生物群落中与艾滋病毒相关的重大破坏,这对人类健康至关重要
并参与许多代谢和免疫相互作用。我们从撒哈拉以南非洲的初步数据
人口,承担着巨大的负担艾滋病毒和相关的心血管疾病,表明有明显的转变,
微生物群落,并且这些对应于全身炎症的增加的测量。独立
在HIV感染后,肠道微生物群落的变化已被证明会产生炎症代谢物,
引起巨噬细胞和血小板活化、血栓形成和动脉斑块形成。我们建议研究
撒哈拉以南非洲人群中与HIV相关的肠道微生物变化并测量全身免疫
与这些变化相关的激活和心血管结局。我们将在体外和体内
研究HIV相关肠道微生物群落变化之间因果关系的模型
和CVD。为了实现这一目标,我们将肠道细胞模型暴露于感兴趣的HIV相关微生物,
测量对这些微生物的炎症反应。我们还将移植小鼠模型,
动脉粥样硬化与粪便微生物群落,然后量化这些诱导的CVD的发展
社区.我们希望这项工作将确定肠道微生物群落可能
有助于慢性HIV的CVD发病机制,并为治疗干预提供机会,
延长艾滋病毒感染者的寿命并提高其生活质量。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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David Benjamin Gootenberg其他文献
David Benjamin Gootenberg的其他文献
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{{ truncateString('David Benjamin Gootenberg', 18)}}的其他基金
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
- 批准号:
9271428 - 财政年份:2017
- 资助金额:
$ 5万 - 项目类别:
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