Circulating LPS from gut microbiota leverages stenosis-induced deep vein thrombosis in mice
Abstract Objective and design An accumulating body of evidence has shown that gut microbiota is involved in regulating inflammation; however, it remains undetermined if and how gut microbiota plays an important role in modulating deep venous thrombosis (DVT), which is an inflammation-involved thromb...
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BMC
2023-06-01
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Series: | Thrombosis Journal |
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Online Access: | https://doi.org/10.1186/s12959-023-00514-2 |
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author | Cheng Liu Ying Zhou Huihui Gao Zeping Zhang Yu Zhou Zifeng Xu Chenhong Zhang Zhen Xu Huajun Zheng Yan-Qing Ma |
author_facet | Cheng Liu Ying Zhou Huihui Gao Zeping Zhang Yu Zhou Zifeng Xu Chenhong Zhang Zhen Xu Huajun Zheng Yan-Qing Ma |
author_sort | Cheng Liu |
collection | DOAJ |
description | Abstract Objective and design An accumulating body of evidence has shown that gut microbiota is involved in regulating inflammation; however, it remains undetermined if and how gut microbiota plays an important role in modulating deep venous thrombosis (DVT), which is an inflammation-involved thrombotic event. Subjects Mice under different treatments were used in this study. Methods and treatment We induced stenosis DVT in mice by partially ligating the inferior vena cava. Mice were treated with antibiotics, prebiotics, probiotics, or inflammatory reagents to modulate inflammatory states, and their effects on the levels of circulating LPS and DVT were examined. Results Antibiotic-treated mice or germ-free mice exhibited compromised DVT. Treatment of mice with either prebiotics or probiotics effectively suppressed DVT, which was accompanied with the downregulation of circulating LPS. Restoration of circulating LPS in these mice with a low dose of LPS was able to restore DVT. LPS-induced DVT was blocked by a TLR4 antagonist. By performing proteomic analysis, we identified TSP1 as one of the downstream effectors of circulating LPS in DVT. Conclusion These results suggest that gut microbiota may play a nonnegligible role in modulating DVT by leveraging the levels of LPS in circulation, thus shedding light on the development of gut microbiota-based strategies for preventing and treating DVT. |
first_indexed | 2024-03-13T01:53:33Z |
format | Article |
id | doaj.art-7ebe1be6314e4218adad394e343d3414 |
institution | Directory Open Access Journal |
issn | 1477-9560 |
language | English |
last_indexed | 2024-03-13T01:53:33Z |
publishDate | 2023-06-01 |
publisher | BMC |
record_format | Article |
series | Thrombosis Journal |
spelling | doaj.art-7ebe1be6314e4218adad394e343d34142023-07-02T11:23:25ZengBMCThrombosis Journal1477-95602023-06-0121111110.1186/s12959-023-00514-2Circulating LPS from gut microbiota leverages stenosis-induced deep vein thrombosis in miceCheng Liu0Ying Zhou1Huihui Gao2Zeping Zhang3Yu Zhou4Zifeng Xu5Chenhong Zhang6Zhen Xu7Huajun Zheng8Yan-Qing Ma9Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life SciencesCollaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life SciencesCollaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life SciencesCollaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life SciencesCollaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life SciencesDepartment of General Surgery, School of Medicine, Ruijin Hospital, Shanghai Jiaotong UniversityState Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiaotong UniversityVersiti Blood Research InstituteNHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan UniversityVersiti Blood Research InstituteAbstract Objective and design An accumulating body of evidence has shown that gut microbiota is involved in regulating inflammation; however, it remains undetermined if and how gut microbiota plays an important role in modulating deep venous thrombosis (DVT), which is an inflammation-involved thrombotic event. Subjects Mice under different treatments were used in this study. Methods and treatment We induced stenosis DVT in mice by partially ligating the inferior vena cava. Mice were treated with antibiotics, prebiotics, probiotics, or inflammatory reagents to modulate inflammatory states, and their effects on the levels of circulating LPS and DVT were examined. Results Antibiotic-treated mice or germ-free mice exhibited compromised DVT. Treatment of mice with either prebiotics or probiotics effectively suppressed DVT, which was accompanied with the downregulation of circulating LPS. Restoration of circulating LPS in these mice with a low dose of LPS was able to restore DVT. LPS-induced DVT was blocked by a TLR4 antagonist. By performing proteomic analysis, we identified TSP1 as one of the downstream effectors of circulating LPS in DVT. Conclusion These results suggest that gut microbiota may play a nonnegligible role in modulating DVT by leveraging the levels of LPS in circulation, thus shedding light on the development of gut microbiota-based strategies for preventing and treating DVT.https://doi.org/10.1186/s12959-023-00514-2Deep venous thrombosisGut microbiotaLPSTSP1PrebioticsProbiotics |
spellingShingle | Cheng Liu Ying Zhou Huihui Gao Zeping Zhang Yu Zhou Zifeng Xu Chenhong Zhang Zhen Xu Huajun Zheng Yan-Qing Ma Circulating LPS from gut microbiota leverages stenosis-induced deep vein thrombosis in mice Thrombosis Journal Deep venous thrombosis Gut microbiota LPS TSP1 Prebiotics Probiotics |
title | Circulating LPS from gut microbiota leverages stenosis-induced deep vein thrombosis in mice |
title_full | Circulating LPS from gut microbiota leverages stenosis-induced deep vein thrombosis in mice |
title_fullStr | Circulating LPS from gut microbiota leverages stenosis-induced deep vein thrombosis in mice |
title_full_unstemmed | Circulating LPS from gut microbiota leverages stenosis-induced deep vein thrombosis in mice |
title_short | Circulating LPS from gut microbiota leverages stenosis-induced deep vein thrombosis in mice |
title_sort | circulating lps from gut microbiota leverages stenosis induced deep vein thrombosis in mice |
topic | Deep venous thrombosis Gut microbiota LPS TSP1 Prebiotics Probiotics |
url | https://doi.org/10.1186/s12959-023-00514-2 |
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