在三个处于不同疾病阶段的 HIV 队列中，微生物代谢产物三甲胺 N-氧化物与炎症和微生物失调有关。
The microbial metabolite trimethylamine-N-oxide in association with inflammation and microbial dysregulation in three HIV cohorts at various disease stages.
机构信息
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge.
Science for Life Laboratory, Division of Proteomics and Nanobiotechnology, KTH Royal Institute of Technology, Solna.
出版信息
AIDS. 2018 Jul 31;32(12):1589-1598. doi: 10.1097/QAD.0000000000001813.
OBJECTIVE
HIV-1-infection infers an increased cardiovascular risk where gut dysbiosis and microbial translocation may contribute. We assessed TMAO, a microbial metabolite with atherosclerotic properties, in plasma of HIV-1-infected individuals at different clinical stages in relation to inflammatory markers, cardiovascular events and gut microbiota.
METHODS
Primary HIV-1-infected (n = 17) and chronic HIV-1-infected individuals (n = 22) were sampled before and after ART-initiation. In the chronic HIV-1-cohort, repeated faecal samples were analysed by 16SrRNA gene sequencing. HIV-1-infected individuals on longstanding ART (n = 101) and healthy HIV-1-negative individuals (n = 60), served as controls. TMAO and markers of immune activation were analysed by LC/MS/MS and immune assays, respectively.
RESULTS
TMAO levels were lower in untreated HIV-1-infected individuals, increased significantly after ART-initiation (P = 0.040 and P < 0.001) but remained similar to healthy controls. TMAO levels were not affected by ART, immune status or degree of systemic inflammation. Higher TMAO in HIV-1-infected individuals on longstanding ART was not significantly associated with cardiovascular risk (P = 0.38). Additionally, TMAO levels correlated inversely with Bacteroidetes (Rho: -0.62, P = 0.002), and positively with Firmicutes (Rho: 0.65, P = 0.001) but held no correlation to TMA-producing genera. Notably gut dysbiosis at follow-up was more pronounced in patients without increase in TMAO levels after ART characterized by loss of Bacteroidetes (P = 0.023) and significantly elevated LPS levels (P = 0.01).
CONCLUSION
Our data does not support that TMAO is a significant link between gut dysbiosis and inflammation in HIV-1-infection. We propose that HIV-1, microbial composition and ART disparately confound TMAO levels, thus limiting its role as a cardiovascular risk marker in HIV-1-infected individuals.
目的
HIV-1 感染会增加心血管风险，而肠道菌群失调和微生物易位可能与此有关。我们评估了 TMAO，一种具有动脉粥样硬化特性的微生物代谢产物，在不同临床阶段的 HIV-1 感染个体的血浆中的水平，与炎症标志物、心血管事件和肠道微生物群有关。
方法
在开始 ART 之前和之后，对原发性 HIV-1 感染（n=17）和慢性 HIV-1 感染个体（n=22）进行了采样。在慢性 HIV-1 队列中，通过 16SrRNA 基因测序对重复的粪便样本进行了分析。长期接受 ART 的 HIV-1 感染个体（n=101）和健康的 HIV-1 阴性个体（n=60）作为对照。通过 LC/MS/MS 和免疫测定分别分析 TMAO 和免疫激活标志物。
结果
未经治疗的 HIV-1 感染个体的 TMAO 水平较低，在开始 ART 后显著增加（P=0.040 和 P<0.001），但仍与健康对照组相似。TMAO 水平不受 ART、免疫状态或全身炎症程度的影响。长期接受 ART 的 HIV-1 感染个体中较高的 TMAO 与心血管风险无显著相关性（P=0.38）。此外，TMAO 水平与拟杆菌门呈负相关（Rho：-0.62，P=0.002），与厚壁菌门呈正相关（Rho：0.65，P=0.001），但与产生 TMA 的属没有相关性。值得注意的是，在 ART 后 TMAO 水平没有增加的患者中，随访时肠道菌群失调更为明显，表现为拟杆菌门减少（P=0.023）和 LPS 水平显著升高（P=0.01）。
结论
我们的数据不支持 TMAO 是 HIV-1 感染中肠道菌群失调和炎症之间的重要联系。我们提出，HIV-1、微生物组成和 ART 分别干扰 TMAO 水平，从而限制其作为 HIV-1 感染个体心血管风险标志物的作用。
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