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A Novel Synbiotic Alleviates Autoimmune Hepatitis by Modulating the Gut Microbiota-Liver Axis and Inhibiting the Hepatic TLR4/NF-κB/NLRP3 Signaling Pathway

Autoimmune hepatitis (AIH) is a liver disease characterized by chronic liver inflammation. The intestinal barrier and microbiome play critical roles in AIH progression. AIH treatment remains challenging because first-line drugs have limited efficacy and many side effects. Thus, there is growing inte...

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Autores principales: Kang, Yongbo, Kuang, Xiaoyu, Yan, Huan, Ren, Peng, Yang, Xiaodan, Liu, Haixia, Liu, Qingqing, Yang, Hao, Kang, Xing, Shen, Xiaorong, Tong, Mingwei, Li, Lin, Wang, Xiaohui, Guo, Linzhi, Ma, Jieqiong, Zhang, Fan, Fan, Weiping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134874/
https://www.ncbi.nlm.nih.gov/pubmed/36794950
http://dx.doi.org/10.1128/msystems.01127-22
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author Kang, Yongbo
Kuang, Xiaoyu
Yan, Huan
Ren, Peng
Yang, Xiaodan
Liu, Haixia
Liu, Qingqing
Yang, Hao
Kang, Xing
Shen, Xiaorong
Tong, Mingwei
Li, Lin
Wang, Xiaohui
Guo, Linzhi
Ma, Jieqiong
Zhang, Fan
Fan, Weiping
author_facet Kang, Yongbo
Kuang, Xiaoyu
Yan, Huan
Ren, Peng
Yang, Xiaodan
Liu, Haixia
Liu, Qingqing
Yang, Hao
Kang, Xing
Shen, Xiaorong
Tong, Mingwei
Li, Lin
Wang, Xiaohui
Guo, Linzhi
Ma, Jieqiong
Zhang, Fan
Fan, Weiping
author_sort Kang, Yongbo
collection PubMed
description Autoimmune hepatitis (AIH) is a liver disease characterized by chronic liver inflammation. The intestinal barrier and microbiome play critical roles in AIH progression. AIH treatment remains challenging because first-line drugs have limited efficacy and many side effects. Thus, there is growing interest in developing synbiotic therapies. This study investigated the effects of a novel synbiotic in an AIH mouse model. We found that this synbiotic (Syn) ameliorated liver injury and improved liver function by reducing hepatic inflammation and pyroptosis. The Syn reversed gut dysbiosis, as indicated by an increase in beneficial bacteria (e.g., Rikenella and Alistipes) and a decrease in potentially harmful bacteria (e.g., Escherichia-Shigella) and lipopolysaccharide (LPS)-bearing Gram-negative bacterial levels. The Syn maintained intestinal barrier integrity, reduced LPS, and inhibited the TLR4/NF-κB and NLRP3/Caspase-1 signaling pathway. In addition, microbiome phenotype prediction by BugBase and bacterial functional potential prediction using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) showed that Syn improved gut microbiota function involving inflammatory injury, metabolism, immune response, and pathopoiesia. Furthermore, the new Syn was as effective as prednisone against AIH. Therefore, this novel Syn could be a candidate drug for alleviating AIH through its anti-inflammatory and antipyroptosis properties that relieve endothelial dysfunction and gut dysbiosis. IMPORTANCE Synbiotics can ameliorate liver injury and improve liver function by reducing hepatic inflammation and pyroptosis. Our data indicate that our new Syn not only reverses gut dysbiosis by increasing beneficial bacteria and decreasing lipopolysaccharide (LPS)-bearing Gram-negative bacteria but also maintains intestinal barrier integrity. Thus, its mechanism might be associated with modulating gut microbiota composition and intestinal barrier function by inhibiting the TLR4/NF-κB/NLRP3/pyroptosis signaling pathway in the liver. This Syn is as effective as prednisone in treating AIH without side effects. Based on these findings, this novel Syn represents a potential therapeutic agent for AIH in clinical practice.
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spelling pubmed-101348742023-04-28 A Novel Synbiotic Alleviates Autoimmune Hepatitis by Modulating the Gut Microbiota-Liver Axis and Inhibiting the Hepatic TLR4/NF-κB/NLRP3 Signaling Pathway Kang, Yongbo Kuang, Xiaoyu Yan, Huan Ren, Peng Yang, Xiaodan Liu, Haixia Liu, Qingqing Yang, Hao Kang, Xing Shen, Xiaorong Tong, Mingwei Li, Lin Wang, Xiaohui Guo, Linzhi Ma, Jieqiong Zhang, Fan Fan, Weiping mSystems Research Article Autoimmune hepatitis (AIH) is a liver disease characterized by chronic liver inflammation. The intestinal barrier and microbiome play critical roles in AIH progression. AIH treatment remains challenging because first-line drugs have limited efficacy and many side effects. Thus, there is growing interest in developing synbiotic therapies. This study investigated the effects of a novel synbiotic in an AIH mouse model. We found that this synbiotic (Syn) ameliorated liver injury and improved liver function by reducing hepatic inflammation and pyroptosis. The Syn reversed gut dysbiosis, as indicated by an increase in beneficial bacteria (e.g., Rikenella and Alistipes) and a decrease in potentially harmful bacteria (e.g., Escherichia-Shigella) and lipopolysaccharide (LPS)-bearing Gram-negative bacterial levels. The Syn maintained intestinal barrier integrity, reduced LPS, and inhibited the TLR4/NF-κB and NLRP3/Caspase-1 signaling pathway. In addition, microbiome phenotype prediction by BugBase and bacterial functional potential prediction using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) showed that Syn improved gut microbiota function involving inflammatory injury, metabolism, immune response, and pathopoiesia. Furthermore, the new Syn was as effective as prednisone against AIH. Therefore, this novel Syn could be a candidate drug for alleviating AIH through its anti-inflammatory and antipyroptosis properties that relieve endothelial dysfunction and gut dysbiosis. IMPORTANCE Synbiotics can ameliorate liver injury and improve liver function by reducing hepatic inflammation and pyroptosis. Our data indicate that our new Syn not only reverses gut dysbiosis by increasing beneficial bacteria and decreasing lipopolysaccharide (LPS)-bearing Gram-negative bacteria but also maintains intestinal barrier integrity. Thus, its mechanism might be associated with modulating gut microbiota composition and intestinal barrier function by inhibiting the TLR4/NF-κB/NLRP3/pyroptosis signaling pathway in the liver. This Syn is as effective as prednisone in treating AIH without side effects. Based on these findings, this novel Syn represents a potential therapeutic agent for AIH in clinical practice. American Society for Microbiology 2023-02-16 /pmc/articles/PMC10134874/ /pubmed/36794950 http://dx.doi.org/10.1128/msystems.01127-22 Text en Copyright © 2023 Kang et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Kang, Yongbo
Kuang, Xiaoyu
Yan, Huan
Ren, Peng
Yang, Xiaodan
Liu, Haixia
Liu, Qingqing
Yang, Hao
Kang, Xing
Shen, Xiaorong
Tong, Mingwei
Li, Lin
Wang, Xiaohui
Guo, Linzhi
Ma, Jieqiong
Zhang, Fan
Fan, Weiping
A Novel Synbiotic Alleviates Autoimmune Hepatitis by Modulating the Gut Microbiota-Liver Axis and Inhibiting the Hepatic TLR4/NF-κB/NLRP3 Signaling Pathway
title A Novel Synbiotic Alleviates Autoimmune Hepatitis by Modulating the Gut Microbiota-Liver Axis and Inhibiting the Hepatic TLR4/NF-κB/NLRP3 Signaling Pathway
title_full A Novel Synbiotic Alleviates Autoimmune Hepatitis by Modulating the Gut Microbiota-Liver Axis and Inhibiting the Hepatic TLR4/NF-κB/NLRP3 Signaling Pathway
title_fullStr A Novel Synbiotic Alleviates Autoimmune Hepatitis by Modulating the Gut Microbiota-Liver Axis and Inhibiting the Hepatic TLR4/NF-κB/NLRP3 Signaling Pathway
title_full_unstemmed A Novel Synbiotic Alleviates Autoimmune Hepatitis by Modulating the Gut Microbiota-Liver Axis and Inhibiting the Hepatic TLR4/NF-κB/NLRP3 Signaling Pathway
title_short A Novel Synbiotic Alleviates Autoimmune Hepatitis by Modulating the Gut Microbiota-Liver Axis and Inhibiting the Hepatic TLR4/NF-κB/NLRP3 Signaling Pathway
title_sort novel synbiotic alleviates autoimmune hepatitis by modulating the gut microbiota-liver axis and inhibiting the hepatic tlr4/nf-κb/nlrp3 signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134874/
https://www.ncbi.nlm.nih.gov/pubmed/36794950
http://dx.doi.org/10.1128/msystems.01127-22
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