背景:三甲胺-N-氧化物(TMAO),肠道微生物来源的胆碱代谢产物,越来越多的研究发现与缺血性卒中(IS)相关。然而,TMAO对IS发生的因果作用仍然令人困惑。
方法:我们全面筛选了PubMed的相关临床研究,WebofScience,和Embase。病例对照和队列研究报告了IS患者和健康对照的TMAO水平。根据牛津大学循证医学中心的标准评估偏倚的风险,英国。使用随机效应模型对检索到的出版物进行荟萃分析,以分析TMAO水平与IS事件之间的联系。此外,进行了孟德尔随机化(MR)分析,以研究TMAO对IS的因果影响,与来自全基因组关联研究(GWAS)的TMAO和IS的汇总数据。使用了以下方法:MR-Egger,加权中位数,逆方差加权,简单模式,和加权模式。该研究已在INPLASY(注册号:INPLASY2023100027)中注册。
结果:确定了8项队列或病例对照研究,涵盖2444例和1707例对照。汇总数据表明,与对照组相比,IS患者的TMAO水平更高(平均差:1.97μM;95%置信区间[CI]:0.87,3.07;P=0.0005),而独特的异质性(I2=96%,P<0.00001)。分组分析显示,研究的异质性可能来自研究本身。然而,在本研究的孟德尔随机化分析中未观察到TMAO对IS的因果效应(P>0.05)。
结论:我们证实,IS患者的TMAO水平往往高于健康个体,而我们的MR分析结果不支持TMAO在IS发生中的因果作用.因此,需要更多的研究来更好地了解TMAO水平与IS发病之间的关系。
BACKGROUND: Trimethylamine-N-oxide (TMAO), an intestinal microbiota-derived choline metabolite, has been found to be associated with ischemic stroke (IS) in more and more studies. However, the causal role of TMAO on IS occurrence remains perplexing.
METHODS: We comprehensively screened the related clinical studies on PubMed, Web of Science, and Embase. Case-control and cohort studies that reported the TMAO levels of both IS patients and healthy controls were included, and the risk of bias was assessed according to the criteria by the Centre for Evidence-Based Medicine in Oxford, UK. A meta-analysis of the retrieved publications was performed with a random-effect model to analyze the connection between TMAO levels and IS events. Besides, a Mendelian randomization (MR) analysis was performed to study the causal effect of TMAO on IS, with pooled data of TMAO and IS obtained from genome-wide association studies (GWAS). The following methods were used: MR-Egger, weighted median, inverse-variance weighted, simple mode, and weighted mode. The study has been registered in INPLASY (Registration number: INPLASY2023100027).
RESULTS: Eight cohort or case-control studies covering 2444 cases and 1707 controls were identified. The pooled data indicated that the IS patients tended to have higher TMAO levels compared with the controls (mean difference: 1.97 μM; 95% confidence interval [CI]: 0.87, 3.07; P = 0.0005), while distinctive heterogeneity (I2 = 96%, P < 0.00001) was observed. Sub-group analysis revealed that the heterogeneity of the studies might be derived from the studies themselves. However, no causal effect of TMAO on IS was observed (P > 0.05) in the Mendelian randomization analysis of this study.
CONCLUSIONS: We confirmed that IS patients tend to have higher TMAO levels than healthy individuals, while our findings of MR analysis did not support the causal role of TMAO in IS occurrence. Therefore, more studies are required for a better understanding of the relationship between TMAO levels and IS onset.