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.
AIDS. 2018 Jul 31;32(12):1589-1598. doi: 10.1097/QAD.0000000000001813.
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.
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.
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).
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.
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。
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。
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）。
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。
