Associations between rivaroxaban dose, gut microbiota, and coagulation parameters in a rat model

Rivaroxaban, a direct oral anticoagulant, is widely prescribed for thrombotic disorders, yet growing evidence suggests that gut microbiota may influence its pharmacodynamic effects. This study investigated dose-dependent associations between rivaroxaban administration, gut microbiota composition, and coagulation parameters in a rat model. Twenty-four rats were assigned to control, low-, medium-, and high-dose rivaroxaban groups. After 30 days of administration, 16S rRNA sequencing and plasma coagulation analyses were performed. Rivaroxaban treatment was associated with significant, dose-related alterations in gut microbiota diversity and composition, notably decreasing Allobaculum and increasing Ligilactobacillus faecis abundance. Additionally, Lactobacillus johnsonii exhibited an initial increase followed by a decline at higher doses. Coagulation parameters—prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were prolonged, and fibrinogen (FIB) levels decreased in a dose-dependent manner. Correlation analyses revealed associations between microbial shifts and coagulation indices. These findings indicate associations rather than causation and highlight the need for further mechanistic studies, including models with altered baseline microbiota, to determine whether specific microbial changes modulate rivaroxaban response.