Influence of gut commensals on murine deep vein thrombosis and platelet function

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.

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Artikel online veröffentlicht:
26. Februar 2024