The gut microbes, Enterococcus and Escherichia-Shigella, affect the responses of heart valve replacement patients to the anticoagulant warfarin
The gut microbes, Enterococcus and Escherichia-Shigella, affect the responses of heart valve replacement patients to the anticoagulant warfarin
复制标题
肠道微生物肠球菌和大肠杆菌志贺氏菌影响心脏瓣膜置换术患者对抗凝剂华法林的反应
DOI：
10.1016/j.phrs.2020.104979
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发表时间：
2020-09-01
影响因子：
9.3
通讯作者：
Miao, Liyan
中科院分区：
文献类型：
--
作者：
Wang, Lin;Liu, Linsheng;Miao, Liyan
已经建立了许多基于患者遗传变异的算法，目的是降低华法林给药期间GI出血和血栓栓塞的风险。然而，大约35%的个体华法林敏感性仍然无法解释。很少有华法林算法考虑到肠道微生物群特征。某些微生物群的鉴定将为降低华法林给药期间出血和血栓栓塞的风险提供新的靶点和新的策略。在这项研究中，我们收集了200例接受心脏瓣膜置换术（HVR）的住院患者的血浆和粪便样本，这些患者被分为低反应（LR）、高反应（HR）和正常反应（NR）。在三组之间观察到肠道微生物群的多样性和相对丰度存在显著差异。肠球菌属在HRs中显著富集（P = 1.249e（-11）），而志贺菌属在LR中显著富集（P = 3.189e（-11））。LR组肠道菌群合成VK 2的量明显高于HR组（P = 0.005）。全基因组鸟枪测序表明，与VK生物合成相关的酶和模块的相对丰度在LR中显著高于HR或NR。通过随机森林模型的10倍交叉验证，确定了12个微生物标记。结果提供了一种新的微生物诊断模型，可用于根据患者肠道植物群组成调整华法林剂量。
Numerous algorithms based on patient genetic variants have been established with the aim of reducing the risk of GI bleeding and thromboembolism during warfarin administration. However, approximately 35 % of individual warfarin sensitivity still remains unexplained. Few of warfarin algorithms take into account gut microbiota profiles. The identification of certain microbiome will provide new targets and new strategies for reducing the risk of bleeding and thromboembolism during warfarin administration. In this study, we collected plasma and stool samples from 200 inpatients undergoing heart valve replacement (HVR), which were classified as low responder (LR), high responder (HR) and normal responder (NR). Significant differences were observed in the diversity and relative abundance of the gut microbiota among the three groups. The genus Escherichia-Shigella was enriched significantly in the LRs (P = 3.189e(-11)), while the genus Enterococcus was enriched significantly in the HRs (P = 1.249e(-11)). The amount of VK2 synthesized by gut microbiota in LR group was much higher than that in HR group (P = 0.005). Whole genome shotgun sequencing indicated that the relative abundance of enzymes and modules associated with VK biosynthesis was significantly higher in LRs than in HRs or NRs. The 12 microbial markers were identified through tenfold cross-validation with a random forest model. The results provided a new microbial diagnostic model that can be used to inform modulation of warfarin dosage on the basis of patient intestinal flora composition.