Live combined bifidobacterium attenuates rivaroxaban-associated colonic bleeding in mice: evidence for a substantial gut microbiota-dependent component
Year: 2026
Type: article
Abstract: Rivaroxaban, a direct oral anticoagulant (DOAC), is widely prescribed for the prevention and treatment of thromboembolic disorders. However, its use is associated with an increased risk of gastrointestinal bleeding, the mechanisms of which remain incompletely understood. Effective strategies to relief such bleeding are also lacking. Because the gut microbiota plays a critical role in maintaining intestinal homeostasis, we investigated whether probiotics could mitigate anticoagulant-related bleeding and explored the underlying mechanisms. Using a rivaroxaban-induced mouse model of colonic bleeding, we found that treatment with live combined Bifidobacterium reduced occult blood in the feces, alleviated damage to colon tissue, and lowered serum levels of the inflammatory cytokines tumor necrosis factor-α and chemokine ligand 5. Integrated 16S rRNA sequencing and untargeted metabolomic analyses showed that LCB treatment was accompanied by alterations in the gut microbial community and fecal metabolic profile. Following antibiotic-mediated microbiota depletion, the overall ameliorative effect of LCB was attenuated, although partial responses, including a reduction in CXCL5, were retained. These findings support a substantial microbiota-dependent component of the full ameliorative phenotype. Untargeted metabolomic analysis identified a metabolite feature putatively annotated as anandamide that showed a nominal decrease following rivaroxaban administration and a nominal increase after LCB treatment. However, these differences did not remain significant after false discovery rate (FDR) correction and were therefore considered exploratory. The same feature also showed a nominal increase following LCB treatment in antibiotic-treated mice without corresponding restoration of the overall ameliorative phenotype, suggesting that this metabolic change alone was insufficient to account for the observed effects. To our knowledge, the present study provides initial evidence that LCB administered after the onset of fecal occult bleeding ameliorates rivaroxaban-associated colonic injury in mice. Collectively, these findings suggest that the overall ameliorative effect of LCB has a substantial gut microbiota-dependent component, whereas the putative anandamide signal represents a hypothesis-generating metabolic association that requires targeted quantitative and functional validation.
Source: Frontiers in Pharmacology
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223158650