Alterations in the cecal microbiome of New Zealand White rabbits due to the long-acting anticoagulant rodenticide brodifacoum
Introduction Long-acting anti-coagulant rodenticides (LAARs) are well characterized with respect to inhibition of vitamin K1 synthesis and effects on blood coagulation. However, effects of LAARs on the microbiome have not been explored.Methods We administered brodifacoum (BDF), one of the more poten...
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Taylor & Francis Group
2025-12-01
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| Series: | Toxicology Communications |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/24734306.2025.2500111 |
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| author | Ankur Naqib Intakhar Ahmad Zachary McDonald Sergey Kalinin Jackie Rocha Ankit Tandon Ramanjaneyulu Rayala Leonid Feferman George E. Chlipala Hui Chen Matthew Lindeblad Israel Rubinstein Stefan J. Green Richard B. van Breemen Douglas L. Feinstein |
| author_facet | Ankur Naqib Intakhar Ahmad Zachary McDonald Sergey Kalinin Jackie Rocha Ankit Tandon Ramanjaneyulu Rayala Leonid Feferman George E. Chlipala Hui Chen Matthew Lindeblad Israel Rubinstein Stefan J. Green Richard B. van Breemen Douglas L. Feinstein |
| author_sort | Ankur Naqib |
| collection | DOAJ |
| description | Introduction Long-acting anti-coagulant rodenticides (LAARs) are well characterized with respect to inhibition of vitamin K1 synthesis and effects on blood coagulation. However, effects of LAARs on the microbiome have not been explored.Methods We administered brodifacoum (BDF), one of the more potent LAARs, to adult male New Zealand White rabbits, and carried out 16S RNA sequencing on cecal samples collected after different times. Samples were also obtained from rabbits treated with the bile sequestrant cholestyramine (CSA) which accelerates BDF clearance from the body, and from CSA-only treated rabbits. We collected blood samples after different times and used mass spectroscopy to measure plasma levels of L-arginine and related molecules.Results Changes at both the phylum and genus levels in relative abundance were observed after 2 and 3 days exposure to BDF. The majority of those microbiota changes were prevented by co-treatment with CSA. Identification of metabolic pathways potentially altered by BDF using Picrust2 identified several L-arginine-related pathways. Exposure to BDF caused increases in plasma L-arginine concentration as well as nitrites, suggesting increased activity of nitric oxide synthase. We also observed increases due to BDF in plasma concentrations of L-arginine-related molecules including L-citrulline, L-ornithine, and methylated L-arginines ADMA and NMMA.Conclusion These results demonstrate that LAAR poisoning can induce microbiome dysbiosis and influence metabolic pathways and metabolites involved in inflammation and vasodilation. |
| format | Article |
| id | doaj-art-d428a930df3747909fc041f3559b7bbc |
| institution | OA Journals |
| issn | 2473-4306 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Toxicology Communications |
| spelling | doaj-art-d428a930df3747909fc041f3559b7bbc2025-08-20T01:51:20ZengTaylor & Francis GroupToxicology Communications2473-43062025-12-019110.1080/24734306.2025.2500111Alterations in the cecal microbiome of New Zealand White rabbits due to the long-acting anticoagulant rodenticide brodifacoumAnkur Naqib0Intakhar Ahmad1Zachary McDonald2Sergey Kalinin3Jackie Rocha4Ankit Tandon5Ramanjaneyulu Rayala6Leonid Feferman7George E. Chlipala8Hui Chen9Matthew Lindeblad10Israel Rubinstein11Stefan J. Green12Richard B. van Breemen13Douglas L. Feinstein14Genomics and Microbiome Core Facility, Rush University, Chicago, IL, USADepartment of Anesthesiology, University of Illinois, Chicago, IL, USADepartment of Anesthesiology, University of Illinois, Chicago, IL, USADepartment of Anesthesiology, University of Illinois, Chicago, IL, USADepartment of Anesthesiology, University of Illinois, Chicago, IL, USADepartment of Anesthesiology, University of Illinois, Chicago, IL, USAMass Spectrometry Core, University of Illinois, Chicago, IL, USAResearch Informatics Core, University of Illinois, Chicago, IL, USAResearch Informatics Core, University of Illinois, Chicago, IL, USAMass Spectrometry Core, University of Illinois, Chicago, IL, USAToxicology Research Laboratory, University of Illinois, Chicago, IL, USADepartment of Medicine, University of Illinois, Chicago, IL, USAGenomics and Microbiome Core Facility, Rush University, Chicago, IL, USADepartment of Pharmaceutical Sciences, Linus Pauling Institute, Oregon State University, Corvallis, OR, USADepartment of Anesthesiology, University of Illinois, Chicago, IL, USAIntroduction Long-acting anti-coagulant rodenticides (LAARs) are well characterized with respect to inhibition of vitamin K1 synthesis and effects on blood coagulation. However, effects of LAARs on the microbiome have not been explored.Methods We administered brodifacoum (BDF), one of the more potent LAARs, to adult male New Zealand White rabbits, and carried out 16S RNA sequencing on cecal samples collected after different times. Samples were also obtained from rabbits treated with the bile sequestrant cholestyramine (CSA) which accelerates BDF clearance from the body, and from CSA-only treated rabbits. We collected blood samples after different times and used mass spectroscopy to measure plasma levels of L-arginine and related molecules.Results Changes at both the phylum and genus levels in relative abundance were observed after 2 and 3 days exposure to BDF. The majority of those microbiota changes were prevented by co-treatment with CSA. Identification of metabolic pathways potentially altered by BDF using Picrust2 identified several L-arginine-related pathways. Exposure to BDF caused increases in plasma L-arginine concentration as well as nitrites, suggesting increased activity of nitric oxide synthase. We also observed increases due to BDF in plasma concentrations of L-arginine-related molecules including L-citrulline, L-ornithine, and methylated L-arginines ADMA and NMMA.Conclusion These results demonstrate that LAAR poisoning can induce microbiome dysbiosis and influence metabolic pathways and metabolites involved in inflammation and vasodilation.https://www.tandfonline.com/doi/10.1080/24734306.2025.2500111Rodenticidemicrobiomerabbitcecalargininebile sequestrant |
| spellingShingle | Ankur Naqib Intakhar Ahmad Zachary McDonald Sergey Kalinin Jackie Rocha Ankit Tandon Ramanjaneyulu Rayala Leonid Feferman George E. Chlipala Hui Chen Matthew Lindeblad Israel Rubinstein Stefan J. Green Richard B. van Breemen Douglas L. Feinstein Alterations in the cecal microbiome of New Zealand White rabbits due to the long-acting anticoagulant rodenticide brodifacoum Toxicology Communications Rodenticide microbiome rabbit cecal arginine bile sequestrant |
| title | Alterations in the cecal microbiome of New Zealand White rabbits due to the long-acting anticoagulant rodenticide brodifacoum |
| title_full | Alterations in the cecal microbiome of New Zealand White rabbits due to the long-acting anticoagulant rodenticide brodifacoum |
| title_fullStr | Alterations in the cecal microbiome of New Zealand White rabbits due to the long-acting anticoagulant rodenticide brodifacoum |
| title_full_unstemmed | Alterations in the cecal microbiome of New Zealand White rabbits due to the long-acting anticoagulant rodenticide brodifacoum |
| title_short | Alterations in the cecal microbiome of New Zealand White rabbits due to the long-acting anticoagulant rodenticide brodifacoum |
| title_sort | alterations in the cecal microbiome of new zealand white rabbits due to the long acting anticoagulant rodenticide brodifacoum |
| topic | Rodenticide microbiome rabbit cecal arginine bile sequestrant |
| url | https://www.tandfonline.com/doi/10.1080/24734306.2025.2500111 |
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