Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
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 by Scientific 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
Abstract
BACKGROUND

Emerging evidence has demonstrated that fecal microbiota transplantation (FMT) has a promising therapeutic effect on mice with experimental colitis and patients with ulcerative colitis (UC), although the mechanism of FMT is unclear.

AIM

To evaluate the protective effect of FMT on UC and clarify its potential dependence on the gut microbiota, through association analysis of gut microbiota with colon transcriptome in mice.

METHODS

Dextran sodium sulfate (DSS)-induced experimental colitis was established and fecal microbiota was transplanted by gavage. Severity of colon inflammation was measured by body weight, disease activity index, colon length and histological score. Gut microbiota alteration was analyzed through 16S ribosomal ribonucleic acid sequencing. The differentially expressed genes (DEGs) in the colon were obtained by transcriptome sequencing. The activation status of colonic T lymphocytes in the lamina propria was evaluated by flow cytometry.

RESULTS

Compared with the DSS group, the weight loss, colon length shortening and inflammation were significantly alleviated in the FMT group. The scores of disease activity index and colon histology decreased obviously after FMT. FMT restored the balance of gut microbiota, especially by upregulating the relative abundance of Lactobacillus and downregulating the relative abundance of Clostridium_sensu_stricto_1 and Turicibacter. In the transcriptomic analysis, 128 DEGs intersected after DSS treatment and FMT. Functional annotation analysis suggested that these DEGs were mainly involved in T-lymphocyte activation. In the DSS group, there was an increase in colonic T helper CD4+ and T cytotoxic CD8+ cells by flow cytometry. FMT selectively downregulated the ratio of colonic CD4+ and CD8+ T cells to maintain intestinal homeostasis. Furthermore, Clostri dium_sensu_stricto_1 was significantly related to inflammation-related genes including REG3G, CCL8 and IDO1.

CONCLUSION

FMT ameliorated DSS-induced colitis in mice via regulating the gut microbiota and T-cell modulation.

Keywords: Fecal microbiota transplantation; Colitis; Gut microbiota; Transcriptome sequencing; T lymphocyte

Core Tip: Previous studies shown that inflammatory bowel disease patients received satisfactory efficacy and safety after fecal microbiota transplantation (FMT) treatment. However, the mechanism of FMT remains unclear. Here, we set out animal experiments to explore the role of FMT in dextran sodium sulfate induced colitis in mice based on microbiome and transcriptome analysis.