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.
Keywords: coagulation; fecal microbiota transplant; intestinal microbiome; metabolic syndrome; thrombin generation; thrombosis.
© 2019 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.
Conflict of interest statement
MN is on the Scientific Advisory Board of Caelus Pharmaceuticals, the Netherlands; CHB is the chief strategy officer of MRM Proteomics, Inc; none of these are directly relevant to the current paper. There are no patents, products in development, or marketed products to declare. The other authors declare no competing financial interests.
Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition.Cell Metab. 2017 Oct 3;26(4):611-619.e6. doi: 10.1016/j.cmet.2017.09.008. Cell Metab. 2017. PMID: 28978426
Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time.Gut. 2020 Mar;69(3):502-512. doi: 10.1136/gutjnl-2019-318320. Epub 2019 May 30. Gut. 2020. PMID: 31147381 Free PMC article.
Complete Microbiota Engraftment Is Not Essential for Recovery from Recurrent Clostridium difficile Infection following Fecal Microbiota Transplantation.mBio. 2016 Dec 20;7(6):e01965-16. doi: 10.1128/mBio.01965-16. mBio. 2016. PMID: 27999162 Free PMC article. Clinical Trial.
Standardized Preparation for Fecal Microbiota Transplantation in Pigs.Front Microbiol. 2018 Jun 19;9:1328. doi: 10.3389/fmicb.2018.01328. eCollection 2018. Front Microbiol. 2018. PMID: 29971061 Free PMC article. Review.
Contemporary Applications of Fecal Microbiota Transplantation to Treat Intestinal Diseases in Humans.Arch Med Res. 2017 Nov;48(8):766-773. doi: 10.1016/j.arcmed.2017.11.006. Epub 2017 Nov 26. Arch Med Res. 2017. PMID: 29183720 Review.
- Jonsson AL, Bäckhed F. Role of gut microbiota in atherosclerosis. Nat Rev Cardiol. 2017;14(2):79‐87. - PubMed
- 016.146.327/ZONMW-VIDI grant
- Amsterdam Cardiovascular Sciences MD/PhD grant
- Dutch Heart Foundation CVON IN CONTROL Young Talent Grant 2013
- 204PRO/Genome Canada and Genome British Columbia
- 214PRO/Genome Canada and Genome British Columbia