Copyright
©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Differential analysis of intestinal microbiota and metabolites in mice with dextran sulfate sodium-induced colitis
Jia-Li Wang, Xiao Han, Jun-Xiang Li, Rui Shi, Lei-Lei Liu, Kai Wang, Yu-Ting Liao, Hui Jiang, Yang Zhang, Jun-Cong Hu, Li-Ming Zhang, Lei Shi
Jia-Li Wang, Xiao Han, Hui Jiang, Yang Zhang, Jun-Cong Hu, Li-Ming Zhang, Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
Jia-Li Wang, Xiao Han, Jun-Xiang Li, Rui Shi, Hui Jiang, Yang Zhang, Jun-Cong Hu, Li-Ming Zhang, Lei Shi, Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China
Lei-Lei Liu, College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China
Kai Wang, Department of Emergency, The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
Yu-Ting Liao, Department of Geriatrics, Gulou Hospital of Traditional Chinese Medicine, Beijing 100009, China
Author contributions: Wang JL and Han X have contributed equally to this work, and they are co-first authors; Shi L and Li JX conceived and designed the study; Wang JL and Han X performed major experimental work; Wang JL and Shi R acquired and analyzed the results and edited the manuscript; Liu LL, Wang K, Liao YT, Jiang H, Zhang Y, Hu JC, and Zhang LM performed the experiments and statistical analyses; Shi L and Li JX revised the manuscript; All authors read and approved the final version of the manuscript.
Supported by the 13th Five-Year Plan for National Key R&D Program of China, No. 2018YFC1705405; Scientific Research Innovation Team Project of Beijing University of Chinese Medicine, No. 2019-JYB-TD004; New Faculty Startup Fund Program of BUCM, No. 2022-JYB-XJSJJ078; and National Natural Science Foundation of China, No. 82004113.
Institutional animal care and use committee statement: The animal study was reviewed and approved by the Animal Ethics Committee of Beijing University of Chinese Medicine. All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (certificate No. SCXK-2019-0010, SPF Biotechnology Co., Ltd., Beijing, China; protocol No. BUCM-2020-01162, The Animal Ethics Committee of Beijing University of Chinese Medicine, Beijing, China).
Conflict-of-interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflict of interest.
Data sharing statement: All data are available upon reasonable request from LS, b01350@bucm.edu.cn.
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: Lei Shi, MD, PhD, Research Associate, Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, No. 6 Fangxingyuan Zone 1, Fangzhuang, Fengtai District, Beijing 100078, China. b01350@bucm.edu.cn
Received: July 12, 2022
Peer-review started: July 12, 2022
First decision: September 26, 2022
Revised: October 4, 2022
Accepted: November 2, 2022
Article in press: November 2, 2022
Published online: November 21, 2022
BACKGROUND
Intestinal micro-ecological imbalances impair the intestinal barrier and induce intestinal inflammation, for example, ulcerative colitis (UC). According to the latest research, abnormalities in intestinal microbiota structure and their metabolites play a dominant role in UC progression; in addition, they could affect the mucus barrier based on different factors. Although numerous studies have confirmed the important role of intestinal microbiota in UC pathogenesis, the intricate connection between microbiota and metabolites and mucus barrier in UC occurrence remains unclear, and correlation analyses of differential microbiota and their metabolites under UC are relatively scarce.
AIM
To reveal the differential intestinal microbiota and metabolites in UC pathogenesis and explore more sensitive biomarker compositions.
METHODS
We used the antibiotic combination method to establish intestinal pseudo-aseptic mice; afterward, dextran sulfate sodium (DSS) was applied to establish an acute experimental colitis mice model. Colitis severity, assessed based on disease activity index, colorectal length, colorectal wet weight, and histological lesions, and mucus-related staining (mucopolysaccharide alcian blue and immunofluorescence of mucin), was compared between the pseudo-aseptic and bacterial colitis mice. Finally, differential intestinal microbiota, metabolites, and their association and correlations, were analyzed by 16s rDNA sequencing in combination with non-targeted metabolomics, through gas chromatography-mass spectrometry.
RESULTS
Compared with the pseudo-aseptic mice, intestinal bacteria positive mice were more severely ill and their intestinal mucus loss was more pronounced in DSS-induced colitis (P < 0.05), suggesting that different microbiota and metabolites could cause the different degrees of colitis. Subsequently, we observed that in addition to Klebsiella, and Bacteroides, which were widely associated with colitis, Candidatus Stoquefichus, Anaerobiospirillum, Muribaculum, and Negativibacillus may be involved in protection against colitis. Furthermore, differential metabolites of the microbiota were mainly enriched in the synthesis-related pathways of key structural sequences of mucin. In combination with the mucin-related staining and immunofluorescence results, the findings indicate that the differential microbiota and their metabolites potentially regulate the composition and function of mucus under colitis.
CONCLUSION
Microbiota and their metabolites are major factors regulating the composition and function of mucus, in turn influencing the function and structure of intestinal mucus barrier under colitis. The different microbiota and metabolites identified in the present study could be novel biomarkers for colitis.
Core Tip: We observed that the differences in microbiota and their metabolites can cause different degrees of colitis. The differential metabolites of the microbiota in colitis are mainly enriched in pathways related to the key structural sequence synthesis of mucin, and the different levels of the metabolites lead to differential expression of mucin and mucus. Therefore, the differential metabolites of colitis could regulate the composition and function of mucus. In addition, the differential intestinal microbiota and their metabolites in mice with colitis were largely associated with amino acid and energy metabolism.
