The gut microbes, Enterococcus and Escherichia-Shigella, affect the responses of heart valve replacement patients to the anticoagulant warfarin. (September 2020)

• Record Type: Journal Article
• Authors: Wang, Lin; Liu, Linsheng; Liu, Xiaoxue; Xiang, Min; Zhou, Ling; Huang, Chenrong; Shen, Zhenya; Miao, Liyan
• Is Part Of: Pharmacological research. Volume 159(2020)
• Publication Date: 2020-09
• Subjects: BMI body mass index -- BSA body surface area -- HR high responder -- HRV heart valve replacement -- INR international normalized ratio -- KEGG Kyoto Encyclopedia of Genes and Genomes -- LR low responder -- MicroPITA microbiomes Picking Interesting Taxonomic Abundance -- MK menaquinone -- NR normal responder -- OUTs Operational Taxonomic Units -- PCoA principal co-ordinates analysis -- WSI warfarin sensitivity index; Warfarin -- Gut microbiota -- Vitamin K -- Anticoagulation -- 16S rDNA sequencing -- Whole genome shotgun sequencing; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.104979
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Why HVR patients showed different responses to the anticoagulant warfarin? The gut microbiota may affect responses to anticoagulation therapy in HVR patients. The most influential genera are Enterococcus and Escherichia-Shigella . Highlights: Gut microbe provides new target for reducing the risk of bleeding or thromboembolism during warfarin administration. Escherichia-Shigella in the gut microbiota may impair response to warfarin anticoagulation therapy. Enterococcus in the gut microbiota may enhance warfarin anticoagulation capacity. Abstract: 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.