Muc2 mucin o-glycosylation interacts with enteropathogenic Escherichia coli to influence the development of ulcerative colitis based on the NF-kB signaling pathway
Abstract Background Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine characterized by a compromised intestinal epithelial barrier. Mucin glycans are crucial in preserving barrier function during bacterial infections, although the underlying mechanisms remain largely unexplo...
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04687-2 |
| _version_ | 1797630040493522944 |
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| author | Juan Wei Chunyan Chen Jing Feng Shuping Zhou Xiaoyue Feng Zhao Yang Heng Lu Hui Tao Liuying Li Huabing Xv Ji Xuan Fangyu Wang |
| author_facet | Juan Wei Chunyan Chen Jing Feng Shuping Zhou Xiaoyue Feng Zhao Yang Heng Lu Hui Tao Liuying Li Huabing Xv Ji Xuan Fangyu Wang |
| author_sort | Juan Wei |
| collection | DOAJ |
| description | Abstract Background Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine characterized by a compromised intestinal epithelial barrier. Mucin glycans are crucial in preserving barrier function during bacterial infections, although the underlying mechanisms remain largely unexplored. Methods A cohort comprising 15 patients diagnosed with UC and 15 healthy individuals was recruited. Stool samples were collected to perform 16S rRNA gene sequencing, while biopsy samples were subjected to nanocapillary liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) to assess O-glycosylation. Gene expression was evaluated through qPCR analysis and Western blotting. Furthermore, animal experiments were conducted to investigate the effects of Escherichia coli and/or O-glycan inhibitor benzyl-α-GalNAc on the development of colitis in mice. Results Our findings revealed that the mucus barrier was disrupted during the early stages of UC, while the MUC2 protein content remained unaltered. Additionally, a noteworthy reduction in the o-glycosylation of MUC2 was observed, along with significant changes in the intestinal microbiota during the early stages of UC. These changes included a decrease in intestinal species richness and an increase in the abundance of Escherichia coli (E. coli). Moreover, subsequent to the administration of galactose or o-glycan inhibitor to intestinal epithelial cells, it was observed that the cell culture supernatant had the ability to modify the proliferation and adhesive capacity of E. coli. Furthermore, when pathogenic E. coli or commensal E. coli were cocultured with intestinal epithelium, both strains elicited activation of the NF-KB signaling pathway in epithelial cells and facilitated the expression of serine protease in comparison to the untreated control. Consistently, the inhibition of o-glycans has been observed to enhance the pathogenicity of E. coli in vivo. Furthermore, a correlation has been established between the level of o-glycans and the development of ulcerative colitis. Specifically, a reduction in the O-glycan content of MUC2 cells has been found to increase the virulence of E. coli, thereby compromising the integrity of the intestinal epithelial barrier. Conclusions Together, there exist complex interactions between the intestinal epithelium, o-glycans, and the intestinal microbiota, which may inform the development of novel therapeutic strategies for the treatment of ulcerative colitis. |
| first_indexed | 2024-03-11T11:01:25Z |
| format | Article |
| id | doaj.art-ace55356fde0448fa08f3c99e5e3b073 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-11T11:01:25Z |
| publishDate | 2023-11-01 |
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| series | Journal of Translational Medicine |
| spelling | doaj.art-ace55356fde0448fa08f3c99e5e3b0732023-11-12T12:28:34ZengBMCJournal of Translational Medicine1479-58762023-11-0121111510.1186/s12967-023-04687-2Muc2 mucin o-glycosylation interacts with enteropathogenic Escherichia coli to influence the development of ulcerative colitis based on the NF-kB signaling pathwayJuan Wei0Chunyan Chen1Jing Feng2Shuping Zhou3Xiaoyue Feng4Zhao Yang5Heng Lu6Hui Tao7Liuying Li8Huabing Xv9Ji Xuan10Fangyu Wang11Department of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Gastroenterology and Hepatology, The First School of Clinical Medicine, Southern Medical UniversityDepartment of Gastroenterology and Hepatology, The First School of Clinical Medicine, Southern Medical UniversityDepartment of Gastroenterology and Hepatology, Huainan First People’s Hospital and, First Affiliated Hospital of The Medical College of Anhui, University of Science and TechnologyDepartment of Gastroenterology and Hepatology, Jinling Clinical College of Nanjing Medical UniversityDepartment of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityDepartment of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityAbstract Background Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine characterized by a compromised intestinal epithelial barrier. Mucin glycans are crucial in preserving barrier function during bacterial infections, although the underlying mechanisms remain largely unexplored. Methods A cohort comprising 15 patients diagnosed with UC and 15 healthy individuals was recruited. Stool samples were collected to perform 16S rRNA gene sequencing, while biopsy samples were subjected to nanocapillary liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) to assess O-glycosylation. Gene expression was evaluated through qPCR analysis and Western blotting. Furthermore, animal experiments were conducted to investigate the effects of Escherichia coli and/or O-glycan inhibitor benzyl-α-GalNAc on the development of colitis in mice. Results Our findings revealed that the mucus barrier was disrupted during the early stages of UC, while the MUC2 protein content remained unaltered. Additionally, a noteworthy reduction in the o-glycosylation of MUC2 was observed, along with significant changes in the intestinal microbiota during the early stages of UC. These changes included a decrease in intestinal species richness and an increase in the abundance of Escherichia coli (E. coli). Moreover, subsequent to the administration of galactose or o-glycan inhibitor to intestinal epithelial cells, it was observed that the cell culture supernatant had the ability to modify the proliferation and adhesive capacity of E. coli. Furthermore, when pathogenic E. coli or commensal E. coli were cocultured with intestinal epithelium, both strains elicited activation of the NF-KB signaling pathway in epithelial cells and facilitated the expression of serine protease in comparison to the untreated control. Consistently, the inhibition of o-glycans has been observed to enhance the pathogenicity of E. coli in vivo. Furthermore, a correlation has been established between the level of o-glycans and the development of ulcerative colitis. Specifically, a reduction in the O-glycan content of MUC2 cells has been found to increase the virulence of E. coli, thereby compromising the integrity of the intestinal epithelial barrier. Conclusions Together, there exist complex interactions between the intestinal epithelium, o-glycans, and the intestinal microbiota, which may inform the development of novel therapeutic strategies for the treatment of ulcerative colitis.https://doi.org/10.1186/s12967-023-04687-2Ulcerative colitisIntestinal epitheliumo-glycanEscherichia coliIntestinal epithelial barrierGut microbiota |
| spellingShingle | Juan Wei Chunyan Chen Jing Feng Shuping Zhou Xiaoyue Feng Zhao Yang Heng Lu Hui Tao Liuying Li Huabing Xv Ji Xuan Fangyu Wang Muc2 mucin o-glycosylation interacts with enteropathogenic Escherichia coli to influence the development of ulcerative colitis based on the NF-kB signaling pathway Journal of Translational Medicine Ulcerative colitis Intestinal epithelium o-glycan Escherichia coli Intestinal epithelial barrier Gut microbiota |
| title | Muc2 mucin o-glycosylation interacts with enteropathogenic Escherichia coli to influence the development of ulcerative colitis based on the NF-kB signaling pathway |
| title_full | Muc2 mucin o-glycosylation interacts with enteropathogenic Escherichia coli to influence the development of ulcerative colitis based on the NF-kB signaling pathway |
| title_fullStr | Muc2 mucin o-glycosylation interacts with enteropathogenic Escherichia coli to influence the development of ulcerative colitis based on the NF-kB signaling pathway |
| title_full_unstemmed | Muc2 mucin o-glycosylation interacts with enteropathogenic Escherichia coli to influence the development of ulcerative colitis based on the NF-kB signaling pathway |
| title_short | Muc2 mucin o-glycosylation interacts with enteropathogenic Escherichia coli to influence the development of ulcerative colitis based on the NF-kB signaling pathway |
| title_sort | muc2 mucin o glycosylation interacts with enteropathogenic escherichia coli to influence the development of ulcerative colitis based on the nf kb signaling pathway |
| topic | Ulcerative colitis Intestinal epithelium o-glycan Escherichia coli Intestinal epithelial barrier Gut microbiota |
| url | https://doi.org/10.1186/s12967-023-04687-2 |
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