Prospective Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2024; 30(11): 1572-1587
Published online Mar 21, 2024. doi: 10.3748/wjg.v30.i11.1572
Washed microbiota transplantation for Crohn’s disease: A metagenomic, metatranscriptomic, and metabolomic-based study
Shi-Ju Chen, Da-Ya Zhang, Xia Wu, Fa-Ming Zhang, Bo-Ta Cui, Yi-Hao Huang, Zu-Lun Zhang, Rui Wang, Fei-Hu Bai
Shi-Ju Chen, Da-Ya Zhang, Graduate School, Hainan Medical University, Haikou 571199, Hainan Province, China
Xia Wu, Fa-Ming Zhang, Bo-Ta Cui, Yi-Hao Huang, Zu-Lun Zhang, Rui Wang, Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
Fei-Hu Bai, Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou 570216, Hainan Province, China
Co-first authors: Shi-Ju Chen and Da-Ya Zhang.
Author contributions: Chen SJ and Zhang DY contributed equally to this work; Chen SJ, Zhang DY, Wu X, Zhang FM, Cui BT, and Bai FH participated in the design of this study and performed the statistical analysis; Chen SJ, Zhang DY, Wu X, and Bai FH drafted the manuscript; Huang YH, Zhang ZL and Wang R recruited participants and participated in the data collection; all authors read and approved the final manuscript.
Supported by the Innovation Platform for Academicians of Hainan Province, No. YSPTZX202313; Hainan Province Clinical Medical Center, No. 2021818; Hainan Provincial Health Industry Research Project, No. 22A200078; Hainan Provincial Postgraduate Innovation Research Project, No. Qhyb2022-133; Hainan Medical University Graduate Student Innovative Research Project, No. HYYB2022A18; and Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine, No. 2020-3HIM.
Institutional review board statement: The study was reviewed and approved by the Second Affiliated Hospital of Nanjing Medical University Institutional Review Board [Approval No. (2022-KY-161-01)].
Clinical trial registration statement: This study is registered at ClinicalTrials.gov. The registration identification number is NCT01793831.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Zhang FM conceived the concept of GenFMTer and transendoscopic enteral tubing and devices related to them; the remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Data sharing statement: The datasets generated and/or analysed during the current study are available in the NCBI BioProject database (PRJNA1069244) and MetaboLights repository (MTBLS9421).
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
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: Fei-Hu Bai, PhD, Chief Doctor, Professor, Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, No. 368 Yehai Avenue, Longhua District, Haikou 570216, Hainan Province, China. baifeihu_hy@163.com
Received: January 7, 2024
Peer-review started: January 7, 2024
First decision: February 1, 2024
Revised: February 7, 2024
Accepted: March 6, 2024
Article in press: March 6, 2024
Published online: March 21, 2024
Processing time: 74 Days and 0 Hours
Abstract
BACKGROUND

Fecal microbiota transplantation (FMT) is a promising therapeutic approach for treating Crohn’s disease (CD). The new method of FMT, based on the automatic washing process, was named as washed microbiota transplantation (WMT). Most existing studies have focused on observing the clinical phenomena. However, the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome, metatranscriptome, and metabolome-has not yet been reported.

AIM

To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT.

METHODS

We conducted a prospective, open-label, single-center clinical study. Eleven CD patients underwent WMT. Their clinical responses (defined as a decrease in their CD Activity Index score of > 100 points) and their microbiome (metagenome, metatranscriptome) and metabolome profiles were evaluated three months after the procedure.

RESULTS

Seven of the 11 patients (63.6%) showed an optimal clinical response three months post-WMT. Gut microbiome diversity significantly increased after WMT, consistent with improved clinical symptoms. Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains, such as Faecalibacterium prausnitzii, Roseburia intestinalis, and Escherichia coli. In addition, metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors. However, levels of vital amino acids that may be associated with disease progression (e.g., L-glutamic acid, gamma-glutamyl-leucine, and prolyl-glutamine) were reduced after WMT.

CONCLUSION

WMT demonstrated therapeutic efficacy in CD treatment, likely due to the effective reconstruction of the patient’s microbiome. Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.

Keywords: Crohn’s disease; Clinical trials; Fecal microbiota transplant; Metagenome; Metatranscriptome; Metabolome

Core Tip: Fecal microbiota transplantation (FMT) is a promising therapeutic approach for treating Crohn’s disease (CD). The new method of FMT, based on the automatic washing process, was named as washed microbiota transplantation (WMT). However, most existing studies have focused on observing clinical phenomena. In the present study, we found that the efficacy of WMT in CD may be due to the effective remodeling of the intestinal micro-ecological balance of patients through the combined in-depth analysis of metagenomic, metatranscriptomic, and metabolomic technologies. Multi-omics techniques can effectively help decipher the underlying mechanism of WMT for CD.