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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Frontiers Media S.A.
2023-01-01
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Series: | Frontiers in Cellular and Infection Microbiology |
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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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