From gut to liver: Exploring the crosstalk between gut-liver axis and oxidative stress in metabolic dysfunction-associated steatotic liver disease
Non-alcoholic fatty liver disease (NAFLD), now recognized as metabolic dysfunction-associated steatotic liver disease (MASLD), represents a significant and escalating global health challenge. Its prevalence is intricately linked to obesity, insulin resistance, and other components of the metabolic s...
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| Language: | English |
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Elsevier
2025-01-01
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| Series: | Annals of Hepatology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268125000031 |
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| author | Mi Zhou Jianyu Lv Xinli Chen Yujie Shi Guanqun Chao Shuo Zhang |
| author_facet | Mi Zhou Jianyu Lv Xinli Chen Yujie Shi Guanqun Chao Shuo Zhang |
| author_sort | Mi Zhou |
| collection | DOAJ |
| description | Non-alcoholic fatty liver disease (NAFLD), now recognized as metabolic dysfunction-associated steatotic liver disease (MASLD), represents a significant and escalating global health challenge. Its prevalence is intricately linked to obesity, insulin resistance, and other components of the metabolic syndrome. As our comprehension of MASLD deepens, it has become evident that this condition extends beyond the liver, embodying a complex, multi-systemic disease with hepatic manifestations that mirror the broader metabolic landscape. This comprehensive review delves into the critical interplay between the gut-liver axis and oxidative stress, elucidating their pivotal roles in the etiology and progression of MASLD. Our analysis reveals several key findings: (1) Bile acid dysregulation can trigger oxidative stress through enhanced ROS production in hepatocytes and Kupffer cells, leading to mitochondrial dysfunction and lipid peroxidation; (2) Gut microbiota dysbiosis disrupts intestinal barrier function, allowing increased translocation of endotoxins like LPS, which activate inflammatory pathways through TLR4 signaling and promote oxidative stress via NADPH oxidase activation; (3) The redox-sensitive transcription factors NF-κB and Nrf2 serve as crucial mediators in the gut-liver axis, with NF-κB regulating inflammatory responses and Nrf2 orchestrating antioxidant defenses; (4) Oxidative stress-induced damage to intestinal barrier function creates a destructive feedback loop, further exacerbating liver inflammation and disease progression. These findings highlight the complex interrelationship between gut-liver axis dysfunction and oxidative stress in MASLD pathogenesis, suggesting potential therapeutic targets for disease management. |
| format | Article |
| id | doaj-art-d0c52ca4cf02438e90210484bcc98863 |
| institution | Kabale University |
| issn | 1665-2681 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj-art-d0c52ca4cf02438e90210484bcc988632025-01-30T05:13:51ZengElsevierAnnals of Hepatology1665-26812025-01-01301101777From gut to liver: Exploring the crosstalk between gut-liver axis and oxidative stress in metabolic dysfunction-associated steatotic liver diseaseMi Zhou0Jianyu Lv1Xinli Chen2Yujie Shi3Guanqun Chao4Shuo Zhang5Department of Gastroenterology, Xinhua Hospital of zhejiang Province: The Second Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang, ChinaDepartment of Gastroenterology, Xinhua Hospital of zhejiang Province: The Second Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang, ChinaDepartment of Gastroenterology, Xinhua Hospital of zhejiang Province: The Second Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang, ChinaDepartment of Gastroenterology, Xinhua Hospital of zhejiang Province: The Second Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang, ChinaDepartment of General Practice, Zhejiang University School of Medicine Sir Run Shaw Hospital, ChinaDepartment of Gastroenterology, Xinhua Hospital of zhejiang Province: The Second Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang, China; Corresponding author.Non-alcoholic fatty liver disease (NAFLD), now recognized as metabolic dysfunction-associated steatotic liver disease (MASLD), represents a significant and escalating global health challenge. Its prevalence is intricately linked to obesity, insulin resistance, and other components of the metabolic syndrome. As our comprehension of MASLD deepens, it has become evident that this condition extends beyond the liver, embodying a complex, multi-systemic disease with hepatic manifestations that mirror the broader metabolic landscape. This comprehensive review delves into the critical interplay between the gut-liver axis and oxidative stress, elucidating their pivotal roles in the etiology and progression of MASLD. Our analysis reveals several key findings: (1) Bile acid dysregulation can trigger oxidative stress through enhanced ROS production in hepatocytes and Kupffer cells, leading to mitochondrial dysfunction and lipid peroxidation; (2) Gut microbiota dysbiosis disrupts intestinal barrier function, allowing increased translocation of endotoxins like LPS, which activate inflammatory pathways through TLR4 signaling and promote oxidative stress via NADPH oxidase activation; (3) The redox-sensitive transcription factors NF-κB and Nrf2 serve as crucial mediators in the gut-liver axis, with NF-κB regulating inflammatory responses and Nrf2 orchestrating antioxidant defenses; (4) Oxidative stress-induced damage to intestinal barrier function creates a destructive feedback loop, further exacerbating liver inflammation and disease progression. These findings highlight the complex interrelationship between gut-liver axis dysfunction and oxidative stress in MASLD pathogenesis, suggesting potential therapeutic targets for disease management.http://www.sciencedirect.com/science/article/pii/S1665268125000031Metabolic dysfunction-associated steatotic liver diseaseGut-liver axisOxidative stressBile acidsGut microbiota |
| spellingShingle | Mi Zhou Jianyu Lv Xinli Chen Yujie Shi Guanqun Chao Shuo Zhang From gut to liver: Exploring the crosstalk between gut-liver axis and oxidative stress in metabolic dysfunction-associated steatotic liver disease Annals of Hepatology Metabolic dysfunction-associated steatotic liver disease Gut-liver axis Oxidative stress Bile acids Gut microbiota |
| title | From gut to liver: Exploring the crosstalk between gut-liver axis and oxidative stress in metabolic dysfunction-associated steatotic liver disease |
| title_full | From gut to liver: Exploring the crosstalk between gut-liver axis and oxidative stress in metabolic dysfunction-associated steatotic liver disease |
| title_fullStr | From gut to liver: Exploring the crosstalk between gut-liver axis and oxidative stress in metabolic dysfunction-associated steatotic liver disease |
| title_full_unstemmed | From gut to liver: Exploring the crosstalk between gut-liver axis and oxidative stress in metabolic dysfunction-associated steatotic liver disease |
| title_short | From gut to liver: Exploring the crosstalk between gut-liver axis and oxidative stress in metabolic dysfunction-associated steatotic liver disease |
| title_sort | from gut to liver exploring the crosstalk between gut liver axis and oxidative stress in metabolic dysfunction associated steatotic liver disease |
| topic | Metabolic dysfunction-associated steatotic liver disease Gut-liver axis Oxidative stress Bile acids Gut microbiota |
| url | http://www.sciencedirect.com/science/article/pii/S1665268125000031 |
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