Multiomics reveals metformin’s dual role in gut microbiome remodeling and hepatic metabolic reprogramming for MAFLD intervention
Abstract Metabolic Associated Fatty Liver Disease (MAFLD), previously known as Non-Alcoholic Fatty Liver Disease, is a growing global health issue associated with obesity, type 2 diabetes, and metabolic syndrome. This study investigates the potential of metformin, a common anti-diabetic drug, to slo...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-07557-7 |
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| author | Yuan-dong Sun Hao Zhang Xiao-long Gong Yuan-min Li Ruiqin Han Chun-xiao Zhou Jian-jun Han |
| author_facet | Yuan-dong Sun Hao Zhang Xiao-long Gong Yuan-min Li Ruiqin Han Chun-xiao Zhou Jian-jun Han |
| author_sort | Yuan-dong Sun |
| collection | DOAJ |
| description | Abstract Metabolic Associated Fatty Liver Disease (MAFLD), previously known as Non-Alcoholic Fatty Liver Disease, is a growing global health issue associated with obesity, type 2 diabetes, and metabolic syndrome. This study investigates the potential of metformin, a common anti-diabetic drug, to slow the progression of MAFLD using a multi-omics approach. Male Wistar rats were fed a choline-deficient diet to induce MAFLD and treated with metformin through their drinking water for 48 weeks. We conducted a comprehensive analysis including liver histology, untargeted metabolomics, lipidomics, and gut microbiome profiling to assess the effects of metformin on liver and gut metabolic patterns. Metformin administration led to significant changes in gut microbiome diversity and the abundance of specific microbial species in MAFLD rats. Histological analysis showed that metformin-treated rats had reduced lipid accumulation and fibrosis in the liver compared to untreated MAFLD rats. Metabolomic and lipidomic analyses revealed that metformin corrected abnormal lipid metabolism patterns, reduced hepatic fat deposition, and influenced key metabolic pathways associated with MAFLD progression. Our findings suggest that metformin has a protective role against MAFLD by modulating gut microbiota and liver metabolism, thereby slowing the progression of hepatic fibrosis. This study provides insights into the therapeutic potential of metformin for MAFLD by addressing metabolic pattern disorders and abnormal changes in gut microbial diversity, highlighting its impact on lipid metabolism and gut-liver axis interactions. |
| format | Article |
| id | doaj-art-c814185b9138426ea5e6bb864dada30d |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-c814185b9138426ea5e6bb864dada30d2025-08-20T04:01:24ZengNature PortfolioScientific Reports2045-23222025-07-0115112310.1038/s41598-025-07557-7Multiomics reveals metformin’s dual role in gut microbiome remodeling and hepatic metabolic reprogramming for MAFLD interventionYuan-dong Sun0Hao Zhang1Xiao-long Gong2Yuan-min Li3Ruiqin Han4Chun-xiao Zhou5Jian-jun Han6Xinjiang Medical University Affiliated Cancer HospitalDepartment of Interventional Radiology, Shandong Cancer Hospital and Institute Affiliated Shandong First Medical University and Shandong Academy of Medical SciencesGraduate School of Shandong First Medical UniversityKey Laboratory of Transplant Engineering and Immunology, NHC, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan UniversityDepartment of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDivision of Gynecologic Oncology, University of North Carolina at Chapel HillDepartment of Interventional Radiology, Shandong Cancer Hospital and Institute Affiliated Shandong First Medical University and Shandong Academy of Medical SciencesAbstract Metabolic Associated Fatty Liver Disease (MAFLD), previously known as Non-Alcoholic Fatty Liver Disease, is a growing global health issue associated with obesity, type 2 diabetes, and metabolic syndrome. This study investigates the potential of metformin, a common anti-diabetic drug, to slow the progression of MAFLD using a multi-omics approach. Male Wistar rats were fed a choline-deficient diet to induce MAFLD and treated with metformin through their drinking water for 48 weeks. We conducted a comprehensive analysis including liver histology, untargeted metabolomics, lipidomics, and gut microbiome profiling to assess the effects of metformin on liver and gut metabolic patterns. Metformin administration led to significant changes in gut microbiome diversity and the abundance of specific microbial species in MAFLD rats. Histological analysis showed that metformin-treated rats had reduced lipid accumulation and fibrosis in the liver compared to untreated MAFLD rats. Metabolomic and lipidomic analyses revealed that metformin corrected abnormal lipid metabolism patterns, reduced hepatic fat deposition, and influenced key metabolic pathways associated with MAFLD progression. Our findings suggest that metformin has a protective role against MAFLD by modulating gut microbiota and liver metabolism, thereby slowing the progression of hepatic fibrosis. This study provides insights into the therapeutic potential of metformin for MAFLD by addressing metabolic pattern disorders and abnormal changes in gut microbial diversity, highlighting its impact on lipid metabolism and gut-liver axis interactions.https://doi.org/10.1038/s41598-025-07557-7Metabolic associated fatty liver diseaseLiver cirrhosisMetforminMulti-omicsLiver metabolism |
| spellingShingle | Yuan-dong Sun Hao Zhang Xiao-long Gong Yuan-min Li Ruiqin Han Chun-xiao Zhou Jian-jun Han Multiomics reveals metformin’s dual role in gut microbiome remodeling and hepatic metabolic reprogramming for MAFLD intervention Scientific Reports Metabolic associated fatty liver disease Liver cirrhosis Metformin Multi-omics Liver metabolism |
| title | Multiomics reveals metformin’s dual role in gut microbiome remodeling and hepatic metabolic reprogramming for MAFLD intervention |
| title_full | Multiomics reveals metformin’s dual role in gut microbiome remodeling and hepatic metabolic reprogramming for MAFLD intervention |
| title_fullStr | Multiomics reveals metformin’s dual role in gut microbiome remodeling and hepatic metabolic reprogramming for MAFLD intervention |
| title_full_unstemmed | Multiomics reveals metformin’s dual role in gut microbiome remodeling and hepatic metabolic reprogramming for MAFLD intervention |
| title_short | Multiomics reveals metformin’s dual role in gut microbiome remodeling and hepatic metabolic reprogramming for MAFLD intervention |
| title_sort | multiomics reveals metformin s dual role in gut microbiome remodeling and hepatic metabolic reprogramming for mafld intervention |
| topic | Metabolic associated fatty liver disease Liver cirrhosis Metformin Multi-omics Liver metabolism |
| url | https://doi.org/10.1038/s41598-025-07557-7 |
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