Introduction The commensal microbiota represents a chronic environmental challenge affecting many
inflammatory processes. Although the microbiota’s role on arterial thrombosis and
atherosclerosis has been increasingly recognized, not much is known about the influence
of microbiota on venous thrombosis. The most common type of venous thrombosis is the
deep vein thrombosis (DVT). Endothelial activation has a key role in triggering DVT
resulting in a procoagulant state. Defects on the gut barrier result in an increase
of bacterial products in the circulation via the portal vein, inducing activation
of the vascular endothelium and increased adhesion of leukocytes and platelets.
Method A standardized mouse model to study venous thrombosis in vivo is the inferior vena
cava (IVC) stenosis model. In this study, we applied the IVC model, restricting the
blood flow for 48 hours, to gnotobiotic mice and quantified the thrombus weight of
thrombi from germ-free (GF) and conventionally raised (CONV-R) mice. We performed
thromboelastometry to study whether the blood coagulation capacities were influenced
by microbiota. The effect of microbiota on platelet function was studied ex vivo by
functional assays, such as aggregometry and flow cytometry. In addition, we used calibrated
automated thrombography to study thrombin generation.
Results The absence of microbiota did not result in changed thrombus weight in the stenosed
IVC. Unchanged blood clotting was also confirmed by the ex vivo thromboelastometry
analyses, after analyzing blood from GF and CONV-R mice. However, GF mice showed decreased
aggregation capacities when stimulated by thrombin which was in line with a reduced
P-selectin exposure in flow cytometry following convulxin activation. Interestingly,
tissue factor-induced thrombin generation was also slightly reduced in platelets of
GFmice.
Conclusion Venous thrombosis, primarily initiated by blood stasis and endothelial cell activation,
was not influenced by the gut microbiota in a 48h murine IVC stenosis model. Although
the microbiota influenced platelet activation and thrombin generation ex vivo, this
did not impact venous thrombus weight in our settings.
