Department of Cardiology, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Jiangxi Branch, Center of National Geriatric Disease Clinical Medical Research Center, First Affiliated Hospital of Gannan Medical University, Gannan Medical University, Ganzhou, China.
Department of Emergency, The First Affiliated Hospital of Gannan Medical University, Gannan Medical University, Ganzhou, China.
Front Cell Infect Microbiol. 2023 Mar 24;13:1038472. doi: 10.3389/fcimb.2023.1038472. eCollection 2023.
The imbalance of gut microbiota (GM) is associated with a higher risk of thrombosis in patients with atrial fibrillation (AF). Oral anticoagulants (OACs) have been found to significantly reduce the risk of thromboembolism and increase the risk of bleeding. However, the OAC-induced alterations in gut microbiota in patients with AF remain elusive.
In this study, the microbial composition in 42 AF patients who received long-term OAC treatment (AF-OAC group), 47 AF patients who did not (AF group), and 40 volunteers with the risk of AF (control group) were analyzed by 16S rRNA gene sequencing of fecal bacterial DNA. The metagenomic functional prediction of major bacterial taxa was performed using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software package.
The gut microbiota differed between the AF-OAC and AF groups. The abundance of and decreased in the two disease groups at the genus level, but OACs treatment mitigated the decreasing tendency and increased beneficial bacterial genera, such as . In addition, OACs reduced the abundance of pro-inflammatory taxa on the genus but increased certain potential pathogenic taxa, such as genera , , and . The Subgroup Linear discriminant analysis effect size (LEfSe) analyses revealed that , , and were more abundant in the anticoagulated bleeding AF patients, and were more abundant in the non-anticoagulated-bleeding-AF patients. The neutrophil-to-lymphocyte ratio (NLR) was lower in the AF-OAC group compared with the AF group ( < 0.05). was positively correlated with the NLR and negatively correlated with the CHA2DS2-VASc score ( < 0.05), and the OACs-enriched species ( and ) was positively correlated with the prothrombin time (PT) ( < 0.05). and were negatively associated with bleeding events ( < 0.05).
Our study suggested that OACs might benefit AF patients by reducing the inflammatory response and modulating the composition and abundance of gut microbiota. In particular, OACs increased the abundance of some gut microbiota involved in bleeding and gastrointestinal dysfunction indicating that the exogenous supplementation with and might be a prophylactic strategy for AF-OAC patients to lower the risk of bleeding after anticoagulation.
肠道微生物群（GM）失衡与心房颤动（AF）患者的血栓形成风险增加有关。口服抗凝剂（OAC）已被发现可显著降低血栓栓塞风险并增加出血风险。然而，OAC 诱导的 AF 患者肠道微生物群的改变仍不清楚。
本研究通过粪便细菌 DNA 的 16S rRNA 基因测序，分析了 42 名接受长期 OAC 治疗的 AF 患者（AF-OAC 组）、47 名未接受 OAC 治疗的 AF 患者（AF 组）和 40 名 AF 风险志愿者（对照组）的微生物组成。使用 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States（PICRUSt）软件包对主要细菌分类群的宏基因组功能进行预测。
AF-OAC 组和 AF 组的肠道微生物群不同。在两个疾病组中，属水平的 和 丰度降低，但 OAC 治疗减轻了下降趋势并增加了有益的细菌属，如 。此外，OAC 降低了属水平的促炎分类群的丰度，但增加了某些潜在的致病分类群，如属 、 、和 。亚组线性判别分析效应大小（LEfSe）分析显示，抗凝出血 AF 患者中更丰富的是 、 、和 ，而非抗凝出血 AF 患者中更丰富的是 、 、和 。与 AF 组相比，AF-OAC 组的中性粒细胞与淋巴细胞比值（NLR）较低（ < 0.05）。 与 NLR 呈正相关，与 CHA2DS2-VASc 评分呈负相关（ < 0.05），OAC 富集物种（ 和 ）与凝血酶原时间（PT）呈正相关（ < 0.05）。 和 与出血事件呈负相关（ < 0.05）。
我们的研究表明，OAC 可能通过减轻炎症反应和调节肠道微生物群的组成和丰度使 AF 患者受益。特别是，OAC 增加了一些与出血和胃肠道功能障碍相关的肠道微生物群的丰度，这表明对外源性补充 和 可能是 AF-OAC 患者抗凝后降低出血风险的预防策略。
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