Lingguizhugan decoction improves non-alcoholic steatohepatitis partially by modulating gut microbiota and correlated metabolites

BackgroundLingguizhugan decoction is a traditional Chinese medicine prescription that has been used to improve non-alcoholic fatty liver disease and its progressive form, non-alcoholic steatohepatitis (NASH). However, the anti-NASH effects and underlying mechanisms of Lingguizhugan decoction remain...

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Main Authors: Mingzhe Zhu, Xue Wang, Kai Wang, Zhiqiang Zhao, Yanqi Dang, Guang Ji, Fenghua Li, Wenjun Zhou
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2023.1066053/full
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author Mingzhe Zhu
Mingzhe Zhu
Xue Wang
Xue Wang
Kai Wang
Zhiqiang Zhao
Yanqi Dang
Guang Ji
Fenghua Li
Fenghua Li
Wenjun Zhou
author_facet Mingzhe Zhu
Mingzhe Zhu
Xue Wang
Xue Wang
Kai Wang
Zhiqiang Zhao
Yanqi Dang
Guang Ji
Fenghua Li
Fenghua Li
Wenjun Zhou
author_sort Mingzhe Zhu
collection DOAJ
description BackgroundLingguizhugan decoction is a traditional Chinese medicine prescription that has been used to improve non-alcoholic fatty liver disease and its progressive form, non-alcoholic steatohepatitis (NASH). However, the anti-NASH effects and underlying mechanisms of Lingguizhugan decoction remain unclear.MethodsMale Sprague-Dawley rats were fed a methionine- and choline-deficient (MCD) diet to induce NASH, and then given Lingguizhugan decoction orally for four weeks. NASH indexes were evaluated by histopathological analysis and biochemical parameters including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver triglycerides (TG), etc. Fecal samples of rats were subjected to profile the changes of gut microbiota and metabolites using 16S rRNA sequencing and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS). Bioinformatics was used to identify Lingguizhugan decoction reversed candidates, and Spearman’s correlation analysis was performed to uncover the relationship among gut microbiota, fecal metabolites, and NASH indexes.ResultsFour-week Lingguizhugan decoction treatment ameliorated MCD diet-induced NASH features, as evidenced by improved hepatic steatosis and inflammation, as well as decreased serum AST and ALT levels. Besides, Lingguizhugan decoction partially restored the changes in gut microbial community composition in NASH rats. Meanwhile, the relative abundance of 26 genera was significantly changed in NASH rats, and 11 genera (such as odoribacter, Ruminococcus_1, Ruminococcaceae_UCG-004, etc.) were identified as significantly reversed by Lingguizhugan decoction. Additionally, a total of 99 metabolites were significantly altered in NASH rats, and 57 metabolites (such as TDCA, Glutamic acid, Isocaproic acid, etc.) enriched in different pathways were reversed by Lingguizhugan decoction. Furthermore, Spearman’s correlation analyses revealed that most of the 57 metabolites were significantly correlated with 11 genera and NASH indexes.ConclusionLingguizhugan decoction may exert protective effects on NASH partially by modulating gut microbiota and correlated metabolites.
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spelling doaj.art-83bcf4bd2a084bef80e67cfd47dcdfba2023-01-26T05:16:38ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-01-011310.3389/fcimb.2023.10660531066053Lingguizhugan decoction improves non-alcoholic steatohepatitis partially by modulating gut microbiota and correlated metabolitesMingzhe Zhu0Mingzhe Zhu1Xue Wang2Xue Wang3Kai Wang4Zhiqiang Zhao5Yanqi Dang6Guang Ji7Fenghua Li8Fenghua Li9Wenjun Zhou10Institute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaExperiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaExperiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaExperiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaExperiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaBackgroundLingguizhugan decoction is a traditional Chinese medicine prescription that has been used to improve non-alcoholic fatty liver disease and its progressive form, non-alcoholic steatohepatitis (NASH). However, the anti-NASH effects and underlying mechanisms of Lingguizhugan decoction remain unclear.MethodsMale Sprague-Dawley rats were fed a methionine- and choline-deficient (MCD) diet to induce NASH, and then given Lingguizhugan decoction orally for four weeks. NASH indexes were evaluated by histopathological analysis and biochemical parameters including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver triglycerides (TG), etc. Fecal samples of rats were subjected to profile the changes of gut microbiota and metabolites using 16S rRNA sequencing and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS). Bioinformatics was used to identify Lingguizhugan decoction reversed candidates, and Spearman’s correlation analysis was performed to uncover the relationship among gut microbiota, fecal metabolites, and NASH indexes.ResultsFour-week Lingguizhugan decoction treatment ameliorated MCD diet-induced NASH features, as evidenced by improved hepatic steatosis and inflammation, as well as decreased serum AST and ALT levels. Besides, Lingguizhugan decoction partially restored the changes in gut microbial community composition in NASH rats. Meanwhile, the relative abundance of 26 genera was significantly changed in NASH rats, and 11 genera (such as odoribacter, Ruminococcus_1, Ruminococcaceae_UCG-004, etc.) were identified as significantly reversed by Lingguizhugan decoction. Additionally, a total of 99 metabolites were significantly altered in NASH rats, and 57 metabolites (such as TDCA, Glutamic acid, Isocaproic acid, etc.) enriched in different pathways were reversed by Lingguizhugan decoction. Furthermore, Spearman’s correlation analyses revealed that most of the 57 metabolites were significantly correlated with 11 genera and NASH indexes.ConclusionLingguizhugan decoction may exert protective effects on NASH partially by modulating gut microbiota and correlated metabolites.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1066053/fullLingguizhugan decoctionNASHMCD dietgut microbiotametabolomics
spellingShingle Mingzhe Zhu
Mingzhe Zhu
Xue Wang
Xue Wang
Kai Wang
Zhiqiang Zhao
Yanqi Dang
Guang Ji
Fenghua Li
Fenghua Li
Wenjun Zhou
Lingguizhugan decoction improves non-alcoholic steatohepatitis partially by modulating gut microbiota and correlated metabolites
Frontiers in Cellular and Infection Microbiology
Lingguizhugan decoction
NASH
MCD diet
gut microbiota
metabolomics
title Lingguizhugan decoction improves non-alcoholic steatohepatitis partially by modulating gut microbiota and correlated metabolites
title_full Lingguizhugan decoction improves non-alcoholic steatohepatitis partially by modulating gut microbiota and correlated metabolites
title_fullStr Lingguizhugan decoction improves non-alcoholic steatohepatitis partially by modulating gut microbiota and correlated metabolites
title_full_unstemmed Lingguizhugan decoction improves non-alcoholic steatohepatitis partially by modulating gut microbiota and correlated metabolites
title_short Lingguizhugan decoction improves non-alcoholic steatohepatitis partially by modulating gut microbiota and correlated metabolites
title_sort lingguizhugan decoction improves non alcoholic steatohepatitis partially by modulating gut microbiota and correlated metabolites
topic Lingguizhugan decoction
NASH
MCD diet
gut microbiota
metabolomics
url https://www.frontiersin.org/articles/10.3389/fcimb.2023.1066053/full
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