Copyright
©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Establishment of a chronic biliary disease mouse model with cholecystoduodenal anastomosis for intestinal microbiome preservation
Yunseon Jang, Jung Yeon Kim, Song Yeon Han, Arum Park, So Jeong Baek, Gyurim Lee, Jihee Kang, Hyewon Ryu, Seok-Hwan Kim
Yunseon Jang, Hyewon Ryu, Translational Immunology Institute, Chungnam National University School of Medicine, Daejeon 35015, South Korea
Jung Yeon Kim, Song Yeon Han, Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea
Arum Park, So Jeong Baek, Gyurim Lee, Jihee Kang, AtoGen Co., Ltd., Techno 1-ro, Daejeon 35015, South Korea
Hyewon Ryu, Department of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, South Korea
Seok-Hwan Kim, Department of Surgery, Chungnam National University Hospital, Daejeon 35015, South Korea
Seok-Hwan Kim, Research Institute for Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea
Author contributions: Jang Y, Kim JY, Han SY, Park A, Baek SJ, Lee G, Kang J, Ryu H, Kim SH contributed to the study design and conceptualization; Jang Y was responsible for the experiments and data acquisition; Kim SH helped interpret the data; Jang Y and Kim SH wrote the manuscript; Kim JY, Han SY, Park A, Baek SJ, Lee G, Kang J and Ryu H contributed to data discussion and revision; Kim SH supervised the manuscript preparation. All the authors approved the final version of the manuscript.
Supported by Korea Health Technology R&D Project through the Korea Health Industry Development Institute, Funded by the Ministry of Health & Welfare, Republic of Korea, No. HR20C0025 and No. HI22C1212; and the National Research Foundation of Korea Grant Funded by the Korea Government, No. RS-2023-00238188.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Chungnam National University Hospital.
Institutional animal care and use committee statement: The animal experiments were approved by the Institutional Animal Care and Use Committee of Chungnam National University (No. CNUH-2023-IA0103-00; November 20, 2023).
Conflict-of-interest statement: The authors have declared that no conflict of interests existed.
Data sharing statement: The data reported in this study can be obtained from the corresponding author upon reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to these guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Seok-Hwan Kim, MD, PhD, Assistant Professor, Department of Surgery, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, South Korea.
kjxh7@cnuh.co.kr
Received: September 20, 2024
Revised: October 22, 2024
Accepted: October 30, 2024
Published online: December 14, 2024
Processing time: 62 Days and 6.2 Hours
BACKGROUND
Chronic biliary disease, including cholangitis and cholecystitis, is attributed to ascending infection by intestinal bacteria. Development of a mouse model for bile duct inflammation is imperative for the advancement of novel therapeutic approaches. Current models fail to replicate the harmful bacterial influx to the biliary tract observed in humans and spread of inflammation to the liver. Therefore, we aimed to establish an animal model of biliary disease that faithfully replicates the mechanisms of human diseases.
AIM
To establish a cholecystoduodenal anastomosis model capable of mimicking the mechanisms of ascending infection and inflammation observed in human biliary diseases.
METHODS
We established a mouse biliary disease model by directly connecting the gallbladder and duodenum, enabling ascending infection into the biliary tract without traversing the sphincter of Oddi.
RESULTS
In the cholecystoduodenal anastomosis mouse model, we observed impaired epithelial structure, wall thickening, and macrophage recruitment in the gallbladder. Despite the absence of postoperative antibiotics, we detected no changes in serum proinflammatory cytokine levels, indicating no systemic inflammation. Moreover, patency between the gallbladder and duodenum was confirmed via common bile duct ligation. Injection of patient-derived pathogenic bacteria into bile duct-ligated mice led to ascending infection, which significantly increased proinflammatory cytokine mRNA expression in the liver, duodenum, and ileum. These results indicate that our mouse model exhibited a direct connection between the gallbladder and duodenum, leading to ascending infection and closely mimicking the clinical features of biliary diseases observed in humans.
CONCLUSION
The cholecystoduodenal anastomosis mouse model is an effective chronic biliary disease model with significant relevance in the development of microbiome-based therapies for the prevention and treatment of biliary disease.
Core Tip: This study introduces a novel cholecystoduodenal anastomosis mouse model to replicate the ascending infection and inflammation observed in human biliary diseases without the use of antibiotics. The model demonstrates localized biliary inflammation and microbial dysbiosis, particularly involving Escherichia coli and Enterococcus, closely mimicking human conditions. This model offers a valuable platform for investigating microbiome-based therapies aimed at preventing and treating chronic biliary diseases.
