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Inhibition of NLRP3 attenuates sodium dextran sulfate-induced inflammatory bowel disease through gut microbiota regulation

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, life-threatening inflammatory disease of gastrointestinal tissue characterized by inflammation of the gut. Recent studies have shown that gut microbiota is involved in the pathophysiology of IBD. However, it is unknown whether direct inhibit...

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Autores principales: Wang, Shi-Le, Zhang, Man-Man, Zhou, Han, Su, Guo-Qiang, Ding, Yi, Xu, Guang-Hui, Wang, Xu, Li, Cheng-Fu, Huang, Wei-Feng, Yi, Li-Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Chang Gung University 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10498411/
https://www.ncbi.nlm.nih.gov/pubmed/36758943
http://dx.doi.org/10.1016/j.bj.2023.01.004
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author Wang, Shi-Le
Zhang, Man-Man
Zhou, Han
Su, Guo-Qiang
Ding, Yi
Xu, Guang-Hui
Wang, Xu
Li, Cheng-Fu
Huang, Wei-Feng
Yi, Li-Tao
author_facet Wang, Shi-Le
Zhang, Man-Man
Zhou, Han
Su, Guo-Qiang
Ding, Yi
Xu, Guang-Hui
Wang, Xu
Li, Cheng-Fu
Huang, Wei-Feng
Yi, Li-Tao
author_sort Wang, Shi-Le
collection PubMed
description BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, life-threatening inflammatory disease of gastrointestinal tissue characterized by inflammation of the gut. Recent studies have shown that gut microbiota is involved in the pathophysiology of IBD. However, it is unknown whether direct inhibition of NLR family pyrin domain containing 3 (NLRP3) inflammasome regulates IBD and alters gut microbiota. METHODS: Here, the NLRP3 expression was evaluated in the colon of IBD subjects. Then, we investigated the effects of NLRP3 inhibition by MCC950 on the gut microbiota and IBD-like symptoms induced by dextran sulfate sodium (DSS). RESULTS: Firstly, NLRP3 and IL-1β levels were increased in patients with IBD as compared with healthy individuals. Then, the animal experiment showed that NLRP3 inhibition by MCC950 significantly attenuated IBD-like symptoms such as diarrhea and colonic inflammation in DSS-induced mice. In addition, NLRP3 inhibition inhibited NLRP3/ASC/caspase-1/IL-1β signaling pathway in the colon, which was over-activated by DSS. Furthermore, MCC950 increased the abundance of phylum Firmicutes, decreased the abundance of phylum Bacteroidetes, and increased the Firmicutes/Bacteroidetes ratio, indicating that the inhibition of NLRP3 inflammasome could regulate the abundance of intestinal flora. According to correlation analysis, NLRP3 might produce its functional role in the regulation of oxidation indicators by changing the gut microbiota composition, especially the phylum Bacteroidota, genus Lactobacillus and species Lactobacillus reuteri. CONCLUSIONS: This study suggests that NLRP3 inflammasome inhibition attenuates IBD-like symptoms by regulating gut microbiota, and provides a basis for the clinical application of NLRP3 as a target for the treatment of IBD.
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spelling pubmed-104984112023-09-14 Inhibition of NLRP3 attenuates sodium dextran sulfate-induced inflammatory bowel disease through gut microbiota regulation Wang, Shi-Le Zhang, Man-Man Zhou, Han Su, Guo-Qiang Ding, Yi Xu, Guang-Hui Wang, Xu Li, Cheng-Fu Huang, Wei-Feng Yi, Li-Tao Biomed J Original Article BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, life-threatening inflammatory disease of gastrointestinal tissue characterized by inflammation of the gut. Recent studies have shown that gut microbiota is involved in the pathophysiology of IBD. However, it is unknown whether direct inhibition of NLR family pyrin domain containing 3 (NLRP3) inflammasome regulates IBD and alters gut microbiota. METHODS: Here, the NLRP3 expression was evaluated in the colon of IBD subjects. Then, we investigated the effects of NLRP3 inhibition by MCC950 on the gut microbiota and IBD-like symptoms induced by dextran sulfate sodium (DSS). RESULTS: Firstly, NLRP3 and IL-1β levels were increased in patients with IBD as compared with healthy individuals. Then, the animal experiment showed that NLRP3 inhibition by MCC950 significantly attenuated IBD-like symptoms such as diarrhea and colonic inflammation in DSS-induced mice. In addition, NLRP3 inhibition inhibited NLRP3/ASC/caspase-1/IL-1β signaling pathway in the colon, which was over-activated by DSS. Furthermore, MCC950 increased the abundance of phylum Firmicutes, decreased the abundance of phylum Bacteroidetes, and increased the Firmicutes/Bacteroidetes ratio, indicating that the inhibition of NLRP3 inflammasome could regulate the abundance of intestinal flora. According to correlation analysis, NLRP3 might produce its functional role in the regulation of oxidation indicators by changing the gut microbiota composition, especially the phylum Bacteroidota, genus Lactobacillus and species Lactobacillus reuteri. CONCLUSIONS: This study suggests that NLRP3 inflammasome inhibition attenuates IBD-like symptoms by regulating gut microbiota, and provides a basis for the clinical application of NLRP3 as a target for the treatment of IBD. Chang Gung University 2023-10 2023-02-08 /pmc/articles/PMC10498411/ /pubmed/36758943 http://dx.doi.org/10.1016/j.bj.2023.01.004 Text en © 2023 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 Article
Wang, Shi-Le
Zhang, Man-Man
Zhou, Han
Su, Guo-Qiang
Ding, Yi
Xu, Guang-Hui
Wang, Xu
Li, Cheng-Fu
Huang, Wei-Feng
Yi, Li-Tao
Inhibition of NLRP3 attenuates sodium dextran sulfate-induced inflammatory bowel disease through gut microbiota regulation
title Inhibition of NLRP3 attenuates sodium dextran sulfate-induced inflammatory bowel disease through gut microbiota regulation
title_full Inhibition of NLRP3 attenuates sodium dextran sulfate-induced inflammatory bowel disease through gut microbiota regulation
title_fullStr Inhibition of NLRP3 attenuates sodium dextran sulfate-induced inflammatory bowel disease through gut microbiota regulation
title_full_unstemmed Inhibition of NLRP3 attenuates sodium dextran sulfate-induced inflammatory bowel disease through gut microbiota regulation
title_short Inhibition of NLRP3 attenuates sodium dextran sulfate-induced inflammatory bowel disease through gut microbiota regulation
title_sort inhibition of nlrp3 attenuates sodium dextran sulfate-induced inflammatory bowel disease through gut microbiota regulation
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10498411/
https://www.ncbi.nlm.nih.gov/pubmed/36758943
http://dx.doi.org/10.1016/j.bj.2023.01.004
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