Wu Q, Yuan LW, Yang LC, Zhang YW, Yao HC, Peng LX, Yao BJ, Jiang ZX. Role of gut microbiota in Crohn’s disease pathogenesis: Insights from fecal microbiota transplantation in mouse model. World J Gastroenterol 2024; 30(31): 3689-3704 [PMID: 39193000 DOI: 10.3748/wjg.v30.i31.3689]
Corresponding Author of This Article
Lian-Wen Yuan, PhD, Chief Physician, Professor, Geriatric Surgery of Department of General Surgery, The Second Xiangya Hospital, Central South University, No. 139 Renmin Middle Road, Changsha 410011, Hunan Province, China. yuanlianwen@csu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Qiang Wu, Lian-Wen Yuan, Li-Chao Yang, Ya-Wei Zhang, Heng-Chang Yao, Liang-Xin Peng, Bao-Jia Yao, Zhi-Xian Jiang, Geriatric Surgery of Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Author contributions: Yuan LW and Wu Q conceived and designed the study; Wu Q wrote the first draft of the manuscript; Yuan LW critically revised the manuscript for important intellectual content; Yang LC, Zhang YW, Yao BJ, and Peng LX generated and analyzed the data and participated in drafting the manuscript; Yao HC and Jiang ZX recruited patients to this study and searched relevant literature; and all authors have read and approved the final manuscript.
Supported bythe National Natural Science Foundation of China, No. 82270590.
Institutional review board statement: The study protocol was approved by the Institutional Review Board of The Second Xiangya Hospital, CSU (approval No. 2022-333).
Institutional animal care and use committee statement: The animal use protocol listed below has been reviewed and approved by the Institutional Animal Care and Use Committee (IACUC), The Second Xiangya Hospital, Central South University (approval No. 2022560).
Conflict-of-interest statement: The authors have no conflicts of interest and financial disclosures.
Data sharing statement: All data analyzed in this paper have been provided in the main manuscript and in supplementary documents, and it is permissible to contact the corresponding author to try to obtain it if necessary.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE 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: Lian-Wen Yuan, PhD, Chief Physician, Professor, Geriatric Surgery of Department of General Surgery, The Second Xiangya Hospital, Central South University, No. 139 Renmin Middle Road, Changsha 410011, Hunan Province, China. yuanlianwen@csu.edu.cn
Received: March 1, 2024 Revised: May 24, 2024 Accepted: July 26, 2024 Published online: August 21, 2024 Processing time: 166 Days and 15.8 Hours
Abstract
BACKGROUND
Inflammatory bowel disease, particularly Crohn’s disease (CD), has been associated with alterations in mesenteric adipose tissue (MAT) and the phenomenon termed “creeping fat”. Histopathological evaluations showed that MAT and intestinal tissues were significantly altered in patients with CD, with these tissues characterized by inflammation and fibrosis.
AIM
To evaluate the complex interplay among MAT, creeping fat, inflammation, and gut microbiota in CD.
METHODS
Intestinal tissue and MAT were collected from 12 patients with CD. Histological manifestations and protein expression levels were analyzed to determine lesion characteristics. Fecal samples were collected from five recently treated CD patients and five control subjects and transplanted into mice. The intestinal and mesenteric lesions in these mice, as well as their systemic inflammatory status, were assessed and compared in mice transplanted with fecal samples from CD patients and control subjects.
RESULTS
Pathological examination of MAT showed significant differences between CD-affected and unaffected colons, including significant differences in gut microbiota structure. Fetal microbiota transplantation (FMT) from clinically healthy donors into mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD ameliorated CD symptoms, whereas FMT from CD patients into these mice exacerbated CD symptoms. Notably, FMT influenced intestinal permeability, barrier function, and levels of proinflammatory factors and adipokines. Furthermore, FMT from CD patients intensified fibrotic changes in the colon tissues of mice with TNBS-induced CD.
CONCLUSION
Gut microbiota play a critical role in the histopathology of CD. Targeting MAT and creeping fat may therefore have potential in the treatment of patients with CD.
Core Tip: The present study evaluated the complex interplay among creeping fat, inflammation, and intestinal microbiota involved in the pathogenesis of Crohn’s disease (CD). The intestinal microbiota was found to play a multifaceted role, mediating the properties of creeping fat while affecting the inflammatory and fibrotic phenotypes associated with CD.
