The intestinal microbiome potentially affects thrombin generation in human subjects

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dc.contributor.authorMohammed, Yassene
dc.contributor.authorKootte, Ruud S.
dc.contributor.authorKopatz, Wil F.
dc.contributor.authorBorchers, Christoph H.
dc.contributor.authorBüller, Harry R.
dc.contributor.authorVersteeg, Henri H.
dc.contributor.authorNieuwdorp, Max
dc.contributor.authorvan Mens, Thijs E.
dc.date.accessioned2020-07-06T17:12:38Z
dc.date.copyright2019en_US
dc.date.issued2019
dc.description.abstractBackground: The intestinal microbiome plays a versatile role in the etiology of arterial thrombosis. In venous thrombosis, driven chiefly by plasma coagulation, no such role has yet been established. We hypothesized that the intestinal microbiome composition affects coagulation in humans. Methods: We used healthy donor fecal microbiota transplant (FMT) to experimentally change the microbiome composition in metabolic syndrome patients. Thirty‐five subjects were randomized in a blinded fashion to healthy donor FMT or autologous FMT as a control in a 2:1 ratio. We measured thrombin generation at baseline and after 6 weeks using automated calibrated thrombinography, and we determined plasma abundance of 32 coagulation related proteins using a targeted mass spectrometry‐based quantitative proteomics assay with heavy labeled internal standards. Results: Healthy donor FMT prolonged the thrombinography lag time (median delta 0.0 versus 0.25 minutes, P = .039). The other thrombinography parameters showed no significant difference. Unsupervised cluster analysis suggested overall downregulation of coagulation related plasma proteins in subject clusters containing predominantly subjects that had a metabolic response to healthy donor FMT. FMT treatment status itself showed no clear clustering pattern with up‐ or downregulation, however, and proteins did not cluster according to an apparent biological grouping. Discussion: A single healthy donor FMT tends to modestly suppress the onset thrombin generation in metabolic syndrome patients, representing initial proof‐of‐principle that the intestinal microbiota composition might affect the coagulation system in humans. The findings merit external validation as a role for intestinal microbiota in coagulation can have clinically important implications.en_US
dc.description.embargo2020-12-06
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipMN is supported by a ZONMW‐VIDI grant 2013 (016.146.327) and a Dutch Heart Foundation CVON IN CONTROL Young Talent Grant 2013. The study reported here was additionally supported by Le Ducq consortium grant 17CVD01 and a Novo Nordisk Foundation GUT‐MMM grant 2016. TEvM is supported by an MD/PhD grant from Amsterdam Cardiovascular Sciences. This work was supported by Genome Canada and Genome British Columbia (project codes 204PRO for operations and 214PRO for technology development).en_US
dc.identifier.citationMohammed, Y., Kootte, R. S., Kopatz, W. F., Borchers, C. H., Büller, H. R., Versteeg, H. H., Nieuwdorp, M., & van Mens, T. E. (2019). The intestinal microbiome potentially affects thrombin generation in human subjects. Journal of Thrombosis and Haemostasis, 18(3), 642-650. https://doi.org/10.1111/jth.14699.en_US
dc.identifier.urihttps://doi.org/10.1111/jth.14699
dc.identifier.urihttp://hdl.handle.net/1828/11906
dc.language.isoenen_US
dc.publisherJournal of Thrombosis and Haemostasisen_US
dc.subjectcoagulation
dc.subjectfecal microbiota transplant
dc.subjectintestinal microbiome
dc.subjectmetabolic syndrome
dc.subjectthrombin generation
dc.subjectthrombosis
dc.subjectUVic Genome BC Proteomics Centre
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.subject.departmentDepartment of Biochemistry and Microbiology
dc.titleThe intestinal microbiome potentially affects thrombin generation in human subjectsen_US
dc.typeArticleen_US

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