4.7 Article

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

Journal

PHARMACOLOGICAL RESEARCH
Volume 159, Issue -, Pages -

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2020.104979

Keywords

Warfarin; Gut microbiota; Vitamin K; Anticoagulation; 16S rDNA sequencing; Whole genome shotgun sequencing

Funding

  1. National Science Foundation of China [81773820, 81803628, 81703619]
  2. National Key New Drug Creation Special Programs [2017ZX09304-021]
  3. Jiangsu Provincial Medical Talent [ZDRCA2016048]
  4. Suzhou Key Laboratory of Drug Clinical Research and Personalized Medicine [SZS201719]
  5. Suzhou Science and Technology Bureau Guiding Project [SYSD2017062]
  6. Young and Middle-aged Academic Leaders of Qing-lan Project in Jiangsu Province in 2020
  7. Scientific and Technological Innovation Team Building Program of Suzhou Vocational Health College

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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.

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