Wen X, Wang HG, Zhang MN, Zhang MH, Wang H, Yang XZ. Fecal microbiota transplantation ameliorates experimental colitis via gut microbiota and T-cell modulation. World J Gastroenterol 2021; 27(21): 2834-2849 [PMID: 34135557 DOI: 10.3748/wjg.v27.i21.2834]
Corresponding Author of This Article
Xiao-Zhong Yang, MD, PhD, Chief Doctor, Department of Gastroenterology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, No. 1 Huanghe Road West, Huai'an 223300, Jiangsu Province, China. hayyyxzh@njmu.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/
World J Gastroenterol. Jun 7, 2021; 27(21): 2834-2849 Published online Jun 7, 2021. doi: 10.3748/wjg.v27.i21.2834
Fecal microbiota transplantation ameliorates experimental colitis via gut microbiota and T-cell modulation
Xin Wen, Hong-Gang Wang, Min-Na Zhang, Meng-Hui Zhang, Han Wang, Xiao-Zhong Yang
Xin Wen, Hong-Gang Wang, Min-Na Zhang, Meng-Hui Zhang, Han Wang, Xiao-Zhong Yang, Department of Gastroenterology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai'an 223300, Jiangsu Province, China
Author contributions: Wen X and Wang HG contributed equally to this work; Wen X, Zhang MN, Zhang MH and Wang H performed the experiments; Wen X analyzed the data, prepared figures and contributed to the drafting of the manuscript; Wang HG supervised this work and edited and revised the manuscript; Yang XZ initiated the project, designed the experiments and approved the final version of manuscript; All authors have approved the final version of the manuscript.
Supported byScientific Research Project of Jiangsu Provincial Health Commission, No. H2018082; Huai'an Natural Science Research Project, No. HAB201926; and Scientific Research Project of Translational Medicine Innovation Team of Huai'an First People's Hospital, No. YZHT201905.
Institutional animal care and use committee statement: The animal experimental protocol was approved by experimental animal ethics committee of the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University (Approval No: DW-P-2018-008-01).
Conflict-of-interest statement: The authors declare no conflicts interest.
Data sharing statement: Materials used for the current study are available from the corresponding author on reasonable request.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Zhong Yang, MD, PhD, Chief Doctor, Department of Gastroenterology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, No. 1 Huanghe Road West, Huai'an 223300, Jiangsu Province, China. hayyyxzh@njmu.edu.cn
Received: January 23, 2021 Peer-review started: January 23, 2021 First decision: February 10, 2021 Revised: March 30, 2021 Accepted: April 28, 2021 Article in press: April 28, 2021 Published online: June 7, 2021 Processing time: 124 Days and 6.3 Hours
ARTICLE HIGHLIGHTS
Research background
Ulcerative colitis (UC) is a growing global disease in which gut microbiota dysbiosis plays an important pathogenic role. However, the current drugs for UC treatment are far from optimal. Therefore, alternative safe and effective new treatments need to be developed.
Research motivation
Clinical practice has confirmed the therapeutic value of fecal microbiota transplantation (FMT) in UC, but its mechanism is unknown. Recently, few studies have indicated the regulatory effect of FMT on the expression of genes in intestinal mucosa, suggesting that the therapeutic effect of FMT on UC may be not only the reconstruction of gut microbiota but also the gene regulation after reconstruction.
Research objectives
The aim of the study was to explore the effect and mechanism of FMT on regulating the balance of gut microbiota and anti-inflammation in dextran sulfate sodium (DSS)-induced colitis.
Research methods
Experimental colitis was induced by DSS, then the severity of intestinal inflammation was evaluated by body weight, colon length, disease activity index and histological scores. Gut microbiota alteration was analyzed through 16S rRNA sequencing. Transcriptome sequencing was used to screen differentially expressed genes in colon. The frequency of immune cells in lamina propria were phenotyped by flow cytometry.
Research results
DSS-induced weight loss, colon length shortening, disease activity index score and histological score were significantly alleviated after FMT treatment. 16S rRNA sequencing indicated that FMT up-regulated the relative abundance of Lactobacillus and down-regulated the relative abundance of Clostridium_sensu_stricto_1 and Turicibacter. Transcriptomics-based differential gene analysis showed that FMT could regulate colonic T cell function. Further flow cytometry analysis showed that FMT downregulated the number of colonic CD4+ and CD8+ T cells to maintain intestinal homeostasis. Moreover, we found that the abundance of Clostridium_sensu_stricto_1 was positively correlated with the expression of inflammation-related genes such as REG3G, CCL8 and IDO1.
Research conclusions
FMT alleviated DSS-induced colitis in mice by improving the gut microbiota and regulating T-cell function.
Research perspectives
This study has initially revealed the mechanism of FMT in the treatment of colitis, which will be confirmed by human studies in the future.
