Dynamic Changes and Prognostic Value of Gut Microbiota-Dependent Trimethylamine-N-Oxide in Acute Ischemic Stroke
Dynamic Changes and Prognostic Value of Gut Microbiota-Dependent Trimethylamine-N-Oxide in Acute Ischemic Stroke
复制标题
急性缺血性脑卒中肠道菌群依赖性三甲胺-N-氧化物的动态变化及预后价值
DOI：
10.3389/fneur.2020.00029
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发表时间：
2020-01-31
影响因子：
3.4
通讯作者：
Yin, Jia
中科院分区：
文献类型：
--
作者：
Tan, Chuhong;Wang, Huidi;Yin, Jia
背景：急性缺血性卒中（AIS）是一种动脉粥样硬化性血栓形成疾病。N-氧化三甲胺（TMAO）是一种肠道微生物群依赖性代谢产物，已被证明具有促动脉粥样硬化和促血栓形成作用。然而，TMAO在AIS中的参与仍不清楚。本研究旨在观察AIS患者TMAO的动态变化，并确定TMAO对主要缺血事件和不良功能结局的预后价值。方法：本研究包括204例AIS患者和108例健康对照者。在入院时、入院第2天和第7天抽取用于TMAO分析的血液样品。建立Logistic回归模型和受试者工作特征曲线，以确定TMAO水平与90天和12个月时的主要缺血性事件（缺血性卒中、心肌梗死或缺血性血管事件导致的死亡）以及不利的功能结局（改良兰金量表评分≥3）之间的相关性。结果：AIS治疗前和治疗后24小时内（入院时）TMAO水平无显着变化，但此后显着下降。对数2转换的基线TMAO水平升高与90天[比值比（OR），2.62; 95%置信区间（CI），1.55-4.45; p < 0.001]和12个月[比值比（OR），2.62; 95%置信区间（CI），1.55-4.45; p < 0.001]的风险增加相关。（OR，3.59; 95% CI，2.12-6.09; p < 0.001）主要缺血性事件，以及90天（OR，2.89; 95% CI，1.46-5.71; p = 0.002）和12个月（OR，2.58; 95% CI，1.50-4.46; p = 0.001）不利的功能结局，调整混杂因素后。预测90天和12个月主要缺血事件的基线TMAO水平曲线下面积分别为0.72（95%CI，0.61-0.83; p < 0.001）和0.76（95%CI，0.66-0.85; p < 0.001）。基线TMAO水平提高了传统危险因素、美国国立卫生研究院卒中量表（NIHSS）评分和N末端B型利钠肽（NT-proBNP）水平的预后准确性。结论：TMAO水平随着卒中发作时间的延长而降低。早期TMAO水平升高预示着不良卒中结局，拓宽了TMAO作为独立预后标志物和治疗靶点的潜在临床应用。
Background: Acute ischemic stroke (AIS) is an atherothrombotic disease. Trimethylamine-N-oxide (TMAO), a gut microbiota-dependent metabolite, has been shown to be proatherogenic and prothrombotic. However, the involvement of TMAO in AIS remains unclear. This study aimed to observe the dynamic changes of TMAO in AIS patients and identify the prognostic value of TMAO for major ischemic events and unfavorable functional outcomes. Methods: This study included 204 AIS patients and 108 healthy controls. Blood samples for TMAO analyses were drawn at admission, 2 and 7 days of admission. Logistic regression models and receiver operating characteristic curves were established to identify associations between TMAO levels and major ischemic events (ischemic stroke, myocardial infarction, or death from an ischemic vascular event), as well as unfavorable functional outcomes (modified Rankin Scale score ≥3), at 90 days and 12 months. Results: TMAO levels showed no significant changes before and within 24 h of AIS treatment (at admission) but decreased significantly thereafter. Elevated log2-transformed baseline TMAO levels were associated with increased risks of 90-day [odds ratio (OR), 2.62; 95% confidence interval (CI), 1.55–4.45; p < 0.001] and 12-month (OR, 3.59; 95% CI, 2.12–6.09; p < 0.001) major ischemic events, as well as 90-day (OR, 2.89; 95% CI, 1.46–5.71; p = 0.002) and 12-month (OR, 2.58; 95% CI, 1.50–4.46; p = 0.001) unfavorable functional outcomes, after adjustments for confounding factors. The areas under curve of baseline TMAO levels for predicting 90-day and 12-month major ischemic events were 0.72 (95% CI, 0.61–0.83; p < 0.001) and 0.76 (95% CI, 0.66–0.85; p < 0.001). Baseline TMAO levels improved the prognostic accuracy of conventional risk factors, National Institutes of Health Stroke Scale (NIHSS) score and N-terminal B-type natriuretic peptide (NT-proBNP) level. Conclusions: TMAO levels decreased with time since stroke onset. Elevated TMAO levels at an earlier period portended poor stroke outcomes, broadening the potential clinical utility of TMAO as an independent prognostic marker and therapeutic target.