Gut microbiome signatures linked to HIV-1 reservoir size and viremia control.

Gut microbiome signatures linked to HIV-1 reservoir size and viremia control.
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与HIV-1病毒库大小和病毒血症控制相关的肠道微生物组特征

DOI:
10.1186/s40168-022-01247-6
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发表时间:
2022-04-11
期刊:
影响因子:
15.5
通讯作者:
Paredes, Roger
Paredes, Roger
中科院分区:
生物学1区
文献类型:
--
作者:
Borgognone, Alessandra;Noguera-Julian, Marc;Oriol, Bruna;Noel-Romas, Laura;Ruiz-Riol, Marta;Guillen, Yolanda;Parera, Mariona;Casadella, Maria;Duran, Clara;Puertas, Maria C.;Catala-Moll, Francesc;De Leon, Marlon;Knodel, Samantha;Birse, Kenzie;Manzardo, Christian;Miro, Jose M.;Clotet, Bonaventura;Martinez-Picado, Javier;Molto, Jose;Mothe, Beatriz;Burgener, Adam;Brander, Christian;Paredes, Roger

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在没有抗逆转录病毒治疗(ART)的情况下,肠道微生物组作为免疫介导的HIV-1控制的预测因子的潜在作用仍然未知。在BCN 02临床试验中,将MVA.HIVconsv免疫原与潜伏期逆转剂罗米地辛组合用于早期ART治疗的HIV-1感染个体,23%(3/13)的参与者在监测的ART暂停(MAP)的32周期间显示出持续的低水平血浆病毒血症。在这里,我们提出了一个多组学分析,以确定在BCN 02试验中与HIV-1控制相关的组成和功能肠道微生物组模式。与非控制者相比,MAP期间的病毒血症控制者(控制者)在接种前和整个研究干预期间表现出较高的拟杆菌目/梭菌目比率和较低的微生物基因丰富度。纵向评估表明,控制器的肠道微生物组富含促炎细菌,而产丁酸细菌和产甲烷古菌则减少。功能分析还表明,脂肪酸和脂质生物合成相关的代谢途径显着增加控制器。粪便元蛋白质组分析证实,基线功能差异主要由梭菌驱动。具有高基线拟杆菌/梭菌比率的参与者具有增加的预先存在的免疫激活相关转录物。拟杆菌目/梭菌目比率以及宿主免疫激活特征与HIV-1储库大小呈负相关。目前的概念验证研究表明,拟杆菌目/梭菌目比例是一种新的肠道微生物组特征,与ART中断后的HIV-1储库大小和免疫介导的病毒控制相关。视频摘要在线版本包含补充材料,可在10. 1186/s40168-022-01247-6获得。
The potential role of the gut microbiome as a predictor of immune-mediated HIV-1 control in the absence of antiretroviral therapy (ART) is still unknown. In the BCN02 clinical trial, which combined the MVA.HIVconsv immunogen with the latency-reversing agent romidepsin in early-ART treated HIV-1 infected individuals, 23% (3/13) of participants showed sustained low-levels of plasma viremia during 32 weeks of a monitored ART pause (MAP). Here, we present a multi-omics analysis to identify compositional and functional gut microbiome patterns associated with HIV-1 control in the BCN02 trial. Viremic controllers during the MAP (controllers) exhibited higher Bacteroidales/Clostridiales ratio and lower microbial gene richness before vaccination and throughout the study intervention when compared to non-controllers. Longitudinal assessment indicated that the gut microbiome of controllers was enriched in pro-inflammatory bacteria and depleted in butyrate-producing bacteria and methanogenic archaea. Functional profiling also showed that metabolic pathways related to fatty acid and lipid biosynthesis were significantly increased in controllers. Fecal metaproteome analyses confirmed that baseline functional differences were mainly driven by Clostridiales. Participants with high baseline Bacteroidales/Clostridiales ratio had increased pre-existing immune activation-related transcripts. The Bacteroidales/Clostridiales ratio as well as host immune-activation signatures inversely correlated with HIV-1 reservoir size. The present proof-of-concept study suggests the Bacteroidales/Clostridiales ratio as a novel gut microbiome signature associated with HIV-1 reservoir size and immune-mediated viral control after ART interruption. Video abstract The online version contains supplementary material available at 10.1186/s40168-022-01247-6.
DOI: 10.1097/qai.0000000000000359
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期刊: TRIALS
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发表时间: 2021-01
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发表时间: 2009-07-08
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影响因子: 3
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