The intestinal microbiome potentially affects thrombin generation in human subjects
| Autor: | Max Nieuwdorp, Ruud S. Kootte, Thijs E. van Mens, Wil F. Kopatz, Harry R. Büller, Henri H. Versteeg, Christoph H. Borchers, Yassene Mohammed |
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| Přispěvatelé: | Graduate School, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Experimental Vascular Medicine, ACS - Pulmonary hypertension & thrombosis |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Research Subjects
Quantitative proteomics 030204 cardiovascular system & hematology fecal microbiota transplant metabolic syndrome Feces 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine Humans Microbiome coagulation thrombosis business.industry Thrombin Original Articles Hematology Fecal Microbiota Transplantation medicine.disease Blood proteins intestinal microbiome Gastrointestinal Microbiome Venous thrombosis Targeted mass spectrometry Coagulation thrombin generation Immunology Original Article Metabolic syndrome business |
| Zdroj: | Journal of thrombosis and haemostasis, 18(3), 642-650. Wiley-Blackwell Journal of Thrombosis and Haemostasis |
| ISSN: | 1538-7933 |
| Popis: | Background 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. |
| Databáze: | OpenAIRE |
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