ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1607131
This article is part of the Research TopicNew Progress on the Role of Gut Microbiota in the Incidence and Prevention of Liver DiseasesView all 21 articles
Rivaroxaban alleviates hepatic sinusoidal obstruction syndrome in mice by modulating the gut microbiota and inhibiting the PI3K/Akt signaling pathway
Provisionally accepted
- 1Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, China
- 2Department of Cardiovascular Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
- 3Department of Gastroenterology, Sheng Jing Hospital Affiliated, China Medical University, Shenyang, Liaoning Province, China
- 4Department of Allergy, Sheng Jing Hospital Affiliated, China Medical University, Shenyang, Liaoning Province, China
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Hepatic sinusoidal obstruction syndrome (HSOS) is a vascular liver disease with a high mortality rate, and treatment methods are limited. Rivaroxaban is an oral anticoagulant.This study aimed to investigate the pharmacological effect and potential mechanism of rivaroxaban on HSOS. In this study, we induced an HSOS mouse model in male C57BL/6J mice by oral administration of monocrotaline. The mice were randomly divided into 4 groups: the control group, the rivaroxaban (RIV) group, the monocrotaline (MCT) group, and the monocrotaline + rivaroxaban (MCT+RIV) group.Compared with the MCT group, rivaroxaban alleviated serum biochemical liver function analysis and liver histopathology in the MCT+RIV group. Additionally, 16S rDNA sequencing of the small intestinal contents revealed that, compared with the MCT group, the MCT+RIV group presented increased relative abundances of 2 Allobaculum and Pediococcus but decreased relative abundances of Streptococcus, Staphylococcus, and Candidatus Arthromitus. Mechanistically, integrated analyses, including transcriptomic sequencing of small intestine tissues, real-time qPCR, Western blot analysis of liver tissues, and correlation analysis, have demonstrated that rivaroxaban protects against MCT-HSOS by inhibiting the PI3K/Akt signaling pathway.In addition, antimicrobial cocktail (ABX) treatment eliminated the beneficial effects of rivaroxaban on liver function and histopathological injury, whereas fecal microbiota transplantation (FMT) from rivaroxaban-treated donors significantly ameliorated liver dysfunction and histological damage in MCT-HSOS mice. These findings indicate that rivaroxaban may be a promising therapeutic option for treating HSOS.
Keywords: rivaroxaban, Hepatic sinusoidal obstruction syndrome, Gut Microbiota, Transcriptomic Analysis, liver injury
Received: 07 Apr 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Liu, Cheng, Xia, Sang, Wei, Chang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Bing Chang, Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, China
Quansheng Li, Department of Allergy, Sheng Jing Hospital Affiliated, China Medical University, Shenyang, 110004, Liaoning Province, China
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