Gut microbiota and metabolomics in metabolic dysfunction-associated fatty liver disease: interaction, mechanism, and therapeutic value
The global epidemic of Metabolic dysfunction-associated fatty liver disease (MAFLD) urgently demands breakthroughs in precision medicine strategies. Its pathogenesis centers on the cascade dysregulation of the gut microbiota-metabolite-liver axis: microbial dysbiosis drives hepatic lipid accumulatio...
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Frontiers Media S.A.
2025-07-01
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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.2025.1635638/full |
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| author | Luyu Wang Hongtao Wang Jian Wu Jian Wu Changyi Ji Ying Wang Mengmeng Gu Mengmeng Gu Miaomiao Li Hongwei Yang |
| author_facet | Luyu Wang Hongtao Wang Jian Wu Jian Wu Changyi Ji Ying Wang Mengmeng Gu Mengmeng Gu Miaomiao Li Hongwei Yang |
| author_sort | Luyu Wang |
| collection | DOAJ |
| description | The global epidemic of Metabolic dysfunction-associated fatty liver disease (MAFLD) urgently demands breakthroughs in precision medicine strategies. Its pathogenesis centers on the cascade dysregulation of the gut microbiota-metabolite-liver axis: microbial dysbiosis drives hepatic lipid accumulation and fibrosis by suppressing short-chain fatty acid synthesis, activating the TLR4/NF-κB inflammatory pathway, and disrupting bile acid signaling. Metabolomics further reveals characteristic disturbances including free fatty acid accumulation, aberrantly elevated branched-chain amino acids (independently predictive of hepatic steatosis), and mitochondrial dysfunction, providing a molecular basis for disease stratification. The field of precision diagnosis is undergoing transformative innovation—multi-omics integration combined with AI-driven analysis of liver enzymes and metabolic biomarkers enables non-invasive, ultra-high-accuracy staging of fibrosis. Therapeutic strategies are shifting towards personalization: microbial interventions require matching to patient-specific microbial ecology, drug selection necessitates efficacy and safety prediction, and synthetically engineered “artificial microbial ecosystems” represent a cutting-edge direction. Future efforts must establish a “multi-omics profiling–AI-powered dynamic modeling–clinical validation” closed-loop framework to precisely halt MAFLD progression to cirrhosis and hepatocellular carcinoma by deciphering patient-specific mechanisms. |
| format | Article |
| id | doaj-art-50e5c93d2e47404b97d217cceed3d76b |
| institution | Matheson Library |
| issn | 2235-2988 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-50e5c93d2e47404b97d217cceed3d76b2025-07-23T05:35:39ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-07-011510.3389/fcimb.2025.16356381635638Gut microbiota and metabolomics in metabolic dysfunction-associated fatty liver disease: interaction, mechanism, and therapeutic valueLuyu Wang0Hongtao Wang1Jian Wu2Jian Wu3Changyi Ji4Ying Wang5Mengmeng Gu6Mengmeng Gu7Miaomiao Li8Hongwei Yang9Anhui Province Key Laboratory of Immunology in Chronic Diseases, Research Center of Laboratory, School of Laboratory, Bengbu Medical University, Bengbu, ChinaAnhui Province Key Laboratory of Immunology in Chronic Diseases, Research Center of Laboratory, School of Laboratory, Bengbu Medical University, Bengbu, ChinaDepartment of Clinical Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, ChinaSuzhou Key Laboratory of Intelligent Critical Illness Biomarkers Translational Reserach, Suzhou, Jiangsu, ChinaAnhui Province Key Laboratory of Immunology in Chronic Diseases, Research Center of Laboratory, School of Laboratory, Bengbu Medical University, Bengbu, ChinaDepartment of Infection Management, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, ChinaDepartment of Clinical Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, ChinaSuzhou Key Laboratory of Intelligent Critical Illness Biomarkers Translational Reserach, Suzhou, Jiangsu, ChinaDepartment of Clinical Laboratory, Suzhou BOE Hospital, Suzhou, Jiangsu, ChinaDepartment of Clinical Laboratory, Suzhou BOE Hospital, Suzhou, Jiangsu, ChinaThe global epidemic of Metabolic dysfunction-associated fatty liver disease (MAFLD) urgently demands breakthroughs in precision medicine strategies. Its pathogenesis centers on the cascade dysregulation of the gut microbiota-metabolite-liver axis: microbial dysbiosis drives hepatic lipid accumulation and fibrosis by suppressing short-chain fatty acid synthesis, activating the TLR4/NF-κB inflammatory pathway, and disrupting bile acid signaling. Metabolomics further reveals characteristic disturbances including free fatty acid accumulation, aberrantly elevated branched-chain amino acids (independently predictive of hepatic steatosis), and mitochondrial dysfunction, providing a molecular basis for disease stratification. The field of precision diagnosis is undergoing transformative innovation—multi-omics integration combined with AI-driven analysis of liver enzymes and metabolic biomarkers enables non-invasive, ultra-high-accuracy staging of fibrosis. Therapeutic strategies are shifting towards personalization: microbial interventions require matching to patient-specific microbial ecology, drug selection necessitates efficacy and safety prediction, and synthetically engineered “artificial microbial ecosystems” represent a cutting-edge direction. Future efforts must establish a “multi-omics profiling–AI-powered dynamic modeling–clinical validation” closed-loop framework to precisely halt MAFLD progression to cirrhosis and hepatocellular carcinoma by deciphering patient-specific mechanisms.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1635638/fullmetabolic dysfunction-associated fatty liver disease (MAFLD)gut microbiotametabolomicsgut-liver axisprecision medicine |
| spellingShingle | Luyu Wang Hongtao Wang Jian Wu Jian Wu Changyi Ji Ying Wang Mengmeng Gu Mengmeng Gu Miaomiao Li Hongwei Yang Gut microbiota and metabolomics in metabolic dysfunction-associated fatty liver disease: interaction, mechanism, and therapeutic value Frontiers in Cellular and Infection Microbiology metabolic dysfunction-associated fatty liver disease (MAFLD) gut microbiota metabolomics gut-liver axis precision medicine |
| title | Gut microbiota and metabolomics in metabolic dysfunction-associated fatty liver disease: interaction, mechanism, and therapeutic value |
| title_full | Gut microbiota and metabolomics in metabolic dysfunction-associated fatty liver disease: interaction, mechanism, and therapeutic value |
| title_fullStr | Gut microbiota and metabolomics in metabolic dysfunction-associated fatty liver disease: interaction, mechanism, and therapeutic value |
| title_full_unstemmed | Gut microbiota and metabolomics in metabolic dysfunction-associated fatty liver disease: interaction, mechanism, and therapeutic value |
| title_short | Gut microbiota and metabolomics in metabolic dysfunction-associated fatty liver disease: interaction, mechanism, and therapeutic value |
| title_sort | gut microbiota and metabolomics in metabolic dysfunction associated fatty liver disease interaction mechanism and therapeutic value |
| topic | metabolic dysfunction-associated fatty liver disease (MAFLD) gut microbiota metabolomics gut-liver axis precision medicine |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1635638/full |
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