Investigating the effect of oral microbiome on cognition in HIV-infected chronic cannabis users

研究口腔微生物组对感染艾滋病毒的长期大麻使用者认知的影响

基本信息

  • 批准号:
    10483586
  • 负责人:
  • 金额:
    $ 74.27万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-09-30 至 2027-07-31
  • 项目状态:
    未结题

项目摘要

Project Summary In the context of human immunodeficiency virus (HIV) infection, cannabis use is an important topic and is the most commonly used drug among HIV-infected individuals. Positive and negative effects of cannabis use in the context of HIV have been reported for various biological processes, including cognitive performance and immune function. Reports vary from cannabis enhancing cognitive function to causing synergistic decline in cognition. Thus, the exact role and limits of chronic cannabis use on HIV cognition under immune perturbations remain unclear. The aim of the present study is to investigate the effects of cannabis-associated oral microbiome on neurocognitive performance in HIV disease by focusing on clinical (Aim 1) and preclinical (Aim 2) neuroHIV models. We and other colleagues have found that Actinomyces species bacteria (e.g. A. meyeri and A. odontolyticus) in the oral cavity of humans, are enriched in the saliva from chronic cannabis users compared to non-users and A. meyeri is enriched in HIV-infected individuals compared to uninfected individuals. But oral A. species enrichment was not demonstrable in tabacco smokers or chronic cocaine users. Further, oral enrichment of A. meyeri was associated with younger age of first cannabis use. Here, we aim to investigate if A. species bacteria has a significant role in HIV neuropathogenesis. To achieve this goal, in Specific Aim 1, HIV cannabis users will be assessed to determine the link between cannabis use-associated oral microbiome (i.e., enrichment of A. meyeri) and cognitive performance by focusing on 1) saliva bacteriome and mycobiome and plasma translocation of A. species bacterial antigens; 2) molecular mechanisms of A. species bacteria mediated TLR2 signaling pathway activation in myeloid cells; 3) neurocognitive performance and its association with microbiome. Specific Aim 2 will make use of two well-established transgenic (tg) mouse models of neuroHIV, including the HIV Tg26 tg and the HIV Tat tg mice, to allow us to determine: 1) the chronic effects of THC and CBD exposure on neurocognition and neuropathology; 2) the chronic effects of THC and CBD exposure on enrichment of A. species bacteria and myeloid cell infiltration to the brain under antiretroviral (ART) drugs; and 3) the mechanisms of cannabis-associated A. meyeri bacteria on neurocognition, neuropathology, and endocannabinoid levels. Understanding the role of chronic cannabis use on oral microbiome and it’s effects on neurocognitive performance in HIV disease is critical to determine its therapeutic benefits and limits in the treatment of patients with accelerated central nervous system pathogenesis under traditional combination antiretroviral therapy (cART).
项目摘要 在人类免疫缺陷病毒(艾滋病毒)感染的情况下,大麻使用是一个重要的议题, 艾滋病毒感染者中最常用的药物。使用大麻对儿童的积极和消极影响 HIV背景下的各种生物学过程,包括认知表现和免疫 功能报告从大麻增强认知功能到导致认知协同下降不等。 因此,在免疫干扰下,长期使用大麻对艾滋病毒认知的确切作用和限制仍然存在。 不清楚本研究的目的是调查大麻相关的口腔微生物组对 通过关注临床(目标1)和临床前(目标2)neuroHIV, 模型我们和其他同事发现放线菌属细菌(如A. meyeri和A. 在人类口腔中的溶牙菌斑(dontolyticus),在慢性大麻使用者的唾液中富集, 非使用者和A.与未感染个体相比,meyeri在HIV感染个体中富集。但口服A. 在吸食鸦片者或长期可卡因使用者中,物种富集并不明显。此外,口服浓缩 曲霉meyeri与首次使用大麻的年龄较小有关。在这里,我们的目的是调查,如果A。物种 细菌在HIV神经发病机制中起重要作用。为了实现这一目标,在具体目标1中,艾滋病毒大麻 将对使用者进行评估以确定大麻使用相关的口腔微生物组之间的联系(即,富集 曲霉Meyeri)和认知表现,通过关注1)唾液细菌组和真菌组以及血浆 易位A. 2)A.细菌介导的TLR 2 骨髓细胞中的信号通路激活; 3)神经认知表现及其与微生物组的关联。 具体目标2将利用两种成熟的神经HIV转基因(tg)小鼠模型,包括 HIV Tg 26 tg和HIV达特tg小鼠,以使我们能够确定:1)THC和CBD暴露的慢性影响 对神经认知和神经病理学的影响; 2)THC和CBD暴露对A. 抗逆转录病毒(ART)药物下细菌和骨髓细胞浸润到大脑中; 3)机制 大麻相关的A. Meyeri细菌对神经认知、神经病理学和内源性大麻素水平的影响。 了解慢性大麻使用对口腔微生物组的作用及其对神经认知的影响 在HIV疾病中的表现对于确定其在患者治疗中的治疗益处和局限性至关重要 在传统的联合抗逆转录病毒治疗下, (cART)。

项目成果

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Sylvia Fitting其他文献

Sylvia Fitting的其他文献

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{{ truncateString('Sylvia Fitting', 18)}}的其他基金

In vivo calcium imaging during appetitive learning in HIV Tat transgenic mice exposed to cannabis
暴露于大麻的 HIV Tat 转基因小鼠食欲学习过程中的体内钙成像
  • 批准号:
    10696442
  • 财政年份:
    2023
  • 资助金额:
    $ 74.27万
  • 项目类别:
Investigating the effect of oral microbiome on cognition in HIV-infected chronic cannabis users
研究口腔微生物组对感染艾滋病毒的长期大麻使用者认知的影响
  • 批准号:
    10708001
  • 财政年份:
    2022
  • 资助金额:
    $ 74.27万
  • 项目类别:
Endocannabinoid-mediated neuroprotection in models of neuroAIDS in vivo
体内神经艾滋病模型中内源性大麻素介导的神经保护
  • 批准号:
    10394213
  • 财政年份:
    2018
  • 资助金额:
    $ 74.27万
  • 项目类别:
Endocannabinoid-mediated neuroprotection in models of neuroAIDS in vivo
体内神经艾滋病模型中内源性大麻素介导的神经保护
  • 批准号:
    9906196
  • 财政年份:
    2018
  • 资助金额:
    $ 74.27万
  • 项目类别:
Investigation of endocannabinoid-mediated neuroprotection in models of neuroAIDS
神经艾滋病模型中内源性大麻素介导的神经保护作用的研究
  • 批准号:
    9135623
  • 财政年份:
    2016
  • 资助金额:
    $ 74.27万
  • 项目类别:
Opiate drug abuse & HIV-induced excitotoxicity in striatal neurons
阿片类药物滥用
  • 批准号:
    9064737
  • 财政年份:
    2015
  • 资助金额:
    $ 74.27万
  • 项目类别:
Opiate drug abuse & HIV-induced excitotoxicity in striatal neurons
阿片类药物滥用
  • 批准号:
    8964511
  • 财政年份:
    2015
  • 资助金额:
    $ 74.27万
  • 项目类别:
Opiate drug abuse & HIV-induced excitotoxicity in striatal neurons
阿片类药物滥用
  • 批准号:
    8410974
  • 财政年份:
    2012
  • 资助金额:
    $ 74.27万
  • 项目类别:
Opiate drug abuse & HIV-induced excitotoxicity in striatal neurons
阿片类药物滥用
  • 批准号:
    8586520
  • 财政年份:
    2012
  • 资助金额:
    $ 74.27万
  • 项目类别:
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