Chronic Opioid Administration is Associated with Prevotella-dominated Dysbiosis in SIVmac251 Infected, cART-treated Macaques.
Chronic Opioid Administration is Associated with Prevotella-dominated Dysbiosis in SIVmac251 Infected, cART-treated Macaques.
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DOI：
10.1007/s11481-021-09993-4
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发表时间：
2022-06
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艾滋病毒感染者滥用阿片类药物的风险增加，这是因为艾滋病毒相关慢性疼痛的处方以及注射吸毒仍然是艾滋病毒传播的主要方式。HIV发病机制的特征在于慢性免疫激活和微生物生态失调，以及穿过肠道屏障的易位加剧炎症。尽管并发率很高，但在艾滋病毒和联合抗逆转录病毒治疗（cART）的背景下，对慢性阿片类药物使用期间的微生物组知之甚少。我们最近证明了减少的CD 4 + T细胞库在淋巴组织中，但增加了小胶质细胞/巨噬细胞库在中枢神经系统中使用吗啡治疗，猴免疫缺陷病毒（SIV）感染的恒河猴与病毒血症抑制cART。为了了解吗啡是否会干扰肠-脑轴，在尸检时收集粪便样本，分离DNA，16 S rRNA测序并分析微生物组的变化。我们发现，吗啡治疗导致生态失调，主要特征是拟杆菌门（Bacteroidetes），特别是普雷沃氏菌科（Prevotellaceae）的扩张，以厚壁菌门（Firmicutes）和其他健康微生物群落成员为代价，导致α多样性降低。在普雷沃氏菌科的许多属中，盐水组和吗啡组之间的差异主要是由于普雷沃氏菌_9的相对丰度较高，普雷沃氏菌_9是与人类微生物组中的炎性致病菌Copri最相似的分类群。这些发现加强了先前的研究，表明阿片类药物滥用与生态失调有关，因此，需要进一步的未来研究来阐明HIV和SIV感染期间宿主和阿片类药物滥用之间的复杂相互作用。
People living with the human immunodeficiency virus (HIV) have an elevated risk of opioid misuse due to both prescriptions for HIV-associated chronic pain and because injection drug use remains a primary mode of HIV transmission. HIV pathogenesis is characterized by chronic immune activation and microbial dysbiosis, and translocation across the gut barrier exacerbating inflammation. Despite the high rate of co-occurrence, little is known about the microbiome during chronic opioid use in the context of HIV and combination antiretroviral therapy (cART). We recently demonstrated the reduction of the CD4 + T-cell reservoir in lymphoid tissues but increased in microglia/macrophage reservoirs in CNS by using morphinetreated, simian immunodeficiency virus (SIV)-infected rhesus macaques with viremia suppressed by cART. To understand whether morphine may perturb the gut-brain axis, fecal samples were collected at necropsy, DNA isolated, and 16S rRNA sequenced and changes of the microbiome analyzed. We found that morphine treatment led to dysbiosis, primarily characterized by expansion of Bacteroidetes, particularly Prevotellaceae, at the expense of Firmicutes and other members of healthy microbial communities resulting in a lower α-diversity. Of the many genera in Prevotellaceae, the differences between the saline and morphine group were primarily due to a higher relative abundance of Prevotella_9, the taxa most similar to Prevotella copri, an inflammatory pathobiont in the human microbiome. These findings reinforce previous research showing that opioid abuse is associated with dysbiosis, therefore, warranting additional future research to elucidate the complex interaction between the host and opioid abuse during HIV and SIV infection.