A Novel Synbiotic Alleviates Autoimmune Hepatitis by Modulating the Gut Microbiota-Liver Axis and Inhibiting the Hepatic TLR4/NF-κB/NLRP3 Signaling Pathway
ABSTRACT 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 gro...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2023-04-01
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| Series: | mSystems |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/msystems.01127-22 |
| _version_ | 1797838332822028288 |
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| author | Yongbo Kang Xiaoyu Kuang Huan Yan Peng Ren Xiaodan Yang Haixia Liu Qingqing Liu Hao Yang Xing Kang Xiaorong Shen Mingwei Tong Lin Li Xiaohui Wang Linzhi Guo Jieqiong Ma Fan Zhang Weiping Fan |
| author_facet | Yongbo Kang Xiaoyu Kuang Huan Yan Peng Ren Xiaodan Yang Haixia Liu Qingqing Liu Hao Yang Xing Kang Xiaorong Shen Mingwei Tong Lin Li Xiaohui Wang Linzhi Guo Jieqiong Ma Fan Zhang Weiping Fan |
| author_sort | Yongbo Kang |
| collection | DOAJ |
| description | ABSTRACT 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. |
| first_indexed | 2024-04-09T15:40:13Z |
| format | Article |
| id | doaj.art-c2623196f2f2497e934d00e66e06fed2 |
| institution | Directory Open Access Journal |
| issn | 2379-5077 |
| language | English |
| last_indexed | 2024-04-09T15:40:13Z |
| publishDate | 2023-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSystems |
| spelling | doaj.art-c2623196f2f2497e934d00e66e06fed22023-04-27T13:02:45ZengAmerican Society for MicrobiologymSystems2379-50772023-04-018210.1128/msystems.01127-22A Novel Synbiotic Alleviates Autoimmune Hepatitis by Modulating the Gut Microbiota-Liver Axis and Inhibiting the Hepatic TLR4/NF-κB/NLRP3 Signaling PathwayYongbo Kang0Xiaoyu Kuang1Huan Yan2Peng Ren3Xiaodan Yang4Haixia Liu5Qingqing Liu6Hao Yang7Xing Kang8Xiaorong Shen9Mingwei Tong10Lin Li11Xiaohui Wang12Linzhi Guo13Jieqiong Ma14Fan Zhang15Weiping Fan16Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, ChinaLaboratory of Morphology, Shanxi Medical University, Taiyuan, Shanxi, ChinaLaboratory of Morphology, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, ChinaABSTRACT 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.https://journals.asm.org/doi/10.1128/msystems.01127-22novel synbioticautoimmune hepatitisintestinal permeabilityintestinal florapyroptosis |
| spellingShingle | Yongbo Kang Xiaoyu Kuang Huan Yan Peng Ren Xiaodan Yang Haixia Liu Qingqing Liu Hao Yang Xing Kang Xiaorong Shen Mingwei Tong Lin Li Xiaohui Wang Linzhi Guo Jieqiong Ma Fan Zhang Weiping Fan A Novel Synbiotic Alleviates Autoimmune Hepatitis by Modulating the Gut Microbiota-Liver Axis and Inhibiting the Hepatic TLR4/NF-κB/NLRP3 Signaling Pathway mSystems novel synbiotic autoimmune hepatitis intestinal permeability intestinal flora pyroptosis |
| 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 | novel synbiotic autoimmune hepatitis intestinal permeability intestinal flora pyroptosis |
| url | https://journals.asm.org/doi/10.1128/msystems.01127-22 |
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