Live combined bifidobacterium attenuates rivaroxaban-associated colonic bleeding in mice: evidence for a substantial gut microbiota-dependent component
4 affiliations
- 1Shengli Clinical College of Fujian Medical University, Department of Pharmacy, College of Pharmacy, Fujian Medical University, Fuzhou University Affiliated Provincial Hospital
- 2Longyan City Center for Drug Inspection and Testing
- 3Department of Pathology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital
- 4Shengli Clinical College of Fujian Medical University, Department of Pharmacy, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital
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.
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BibTeX
@article{chen2026live,
title = {{Live combined bifidobacterium attenuates rivaroxaban-associated colonic bleeding in mice: evidence for a substantial gut microbiota-dependent component}},
author = {Xiaowen Chen and Yuze Lin and Youqi Huang and Linghong Zeng and Jie Lin and Min Chen},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1846463},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1846463/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Live combined bifidobacterium attenuates rivaroxaban-associated colonic bleeding in mice: evidence for a substantial gut microbiota-dependent component
AU - Xiaowen Chen
AU - Yuze Lin
AU - Youqi Huang
AU - Linghong Zeng
AU - Jie Lin
AU - Min Chen
PY - 2026
DA - 2026/10/21
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1846463
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1846463/full
AB - 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.
SN - 1663-9812
ER -