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Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Experimental Ulcerative Colitis Mice
Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684163/ https://www.ncbi.nlm.nih.gov/pubmed/35609771 http://dx.doi.org/10.1016/j.gpb.2022.05.002 |
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author | Li, Mingyue Guo, Weina Dong, Yalan Wang, Wenzhu Tian, Chunxia Zhang, Zili Yu, Ting Zhou, Haifeng Gui, Yang Xue, Kaming Li, Junyi Jiang, Feng Sarapultsev, Alexey Wang, Huafang Zhang, Ge Luo, Shanshan Fan, Heng Hu, Desheng |
author_facet | Li, Mingyue Guo, Weina Dong, Yalan Wang, Wenzhu Tian, Chunxia Zhang, Zili Yu, Ting Zhou, Haifeng Gui, Yang Xue, Kaming Li, Junyi Jiang, Feng Sarapultsev, Alexey Wang, Huafang Zhang, Ge Luo, Shanshan Fan, Heng Hu, Desheng |
author_sort | Li, Mingyue |
collection | PubMed |
description | Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model, and addressed the mechanism by which CSR exerts the protective effects. We characterized the therapeutic effects and the potential mechanism of CSR on treating UC using histological staining, intestinal permeability assay, cytokine assay, flow cytometry, fecal microbiota transplantation (FMT), 16S rRNA sequencing, untargeted metabolomics, and cell differentiation. CSR administration significantly ameliorated the dextran sodium sulfate (DSS)-induced colitis in mice, which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index (DAI) score and intestinal permeability. Meanwhile, CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels, and improved the balances of Treg/Th1 and Treg/Th17 to maintain the colonic immune homeostasis. Notably, all the therapeutic effects were exerted in a gut microbiota-dependent manner. Furthermore, CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites, which is probably associated with the gut microbiota-mediated protective effects. In conclusion, this study provides the strong evidence that CSR may be a promising therapeutic drug for UC. |
format | Online Article Text |
id | pubmed-9684163 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-96841632022-11-25 Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Experimental Ulcerative Colitis Mice Li, Mingyue Guo, Weina Dong, Yalan Wang, Wenzhu Tian, Chunxia Zhang, Zili Yu, Ting Zhou, Haifeng Gui, Yang Xue, Kaming Li, Junyi Jiang, Feng Sarapultsev, Alexey Wang, Huafang Zhang, Ge Luo, Shanshan Fan, Heng Hu, Desheng Genomics Proteomics Bioinformatics Original Research Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model, and addressed the mechanism by which CSR exerts the protective effects. We characterized the therapeutic effects and the potential mechanism of CSR on treating UC using histological staining, intestinal permeability assay, cytokine assay, flow cytometry, fecal microbiota transplantation (FMT), 16S rRNA sequencing, untargeted metabolomics, and cell differentiation. CSR administration significantly ameliorated the dextran sodium sulfate (DSS)-induced colitis in mice, which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index (DAI) score and intestinal permeability. Meanwhile, CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels, and improved the balances of Treg/Th1 and Treg/Th17 to maintain the colonic immune homeostasis. Notably, all the therapeutic effects were exerted in a gut microbiota-dependent manner. Furthermore, CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites, which is probably associated with the gut microbiota-mediated protective effects. In conclusion, this study provides the strong evidence that CSR may be a promising therapeutic drug for UC. Elsevier 2022-04 2022-05-21 /pmc/articles/PMC9684163/ /pubmed/35609771 http://dx.doi.org/10.1016/j.gpb.2022.05.002 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Li, Mingyue Guo, Weina Dong, Yalan Wang, Wenzhu Tian, Chunxia Zhang, Zili Yu, Ting Zhou, Haifeng Gui, Yang Xue, Kaming Li, Junyi Jiang, Feng Sarapultsev, Alexey Wang, Huafang Zhang, Ge Luo, Shanshan Fan, Heng Hu, Desheng Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Experimental Ulcerative Colitis Mice |
title | Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Experimental Ulcerative Colitis Mice |
title_full | Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Experimental Ulcerative Colitis Mice |
title_fullStr | Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Experimental Ulcerative Colitis Mice |
title_full_unstemmed | Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Experimental Ulcerative Colitis Mice |
title_short | Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Experimental Ulcerative Colitis Mice |
title_sort | beneficial effects of celastrol on immune balance by modulating gut microbiota in experimental ulcerative colitis mice |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684163/ https://www.ncbi.nlm.nih.gov/pubmed/35609771 http://dx.doi.org/10.1016/j.gpb.2022.05.002 |
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