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The Gut Microbiome and Ferroptosis in MAFLD
Jie Ji1,2, Liwei Wu1,2, Jue Wei3
1Department of Gastroenterology, Putuo People's Hospital, Tongji University, Shanghai, China.
Abstract:
Metabolic-associated fatty liver disease (MAFLD) is a new disease definition, and is proposed to replace the previous name, nonalcoholic fatty liver disease (NAFLD). Globally, MAFLD/NAFLD is the most common liver disease, with an incidence rate ranging from 6% to 35% in adult populations. The pathogenesis of MAFLD/NAFLD is closely related to insulin resistance (IR), and the genetic susceptibility to acquired metabolic stress-associated liver injury. Similarly, the gut microbiota in MAFLD/NAFLD is being revaluated by scientists, as the gut and liver influence each other via the gut-liver axis. Ferroptosis is a novel form of programmed cell death caused by iron-dependent lipid peroxidation. Emerging evidence suggests that ferroptosis has a key role in the pathological progression of MAFLD/NAFLD, and inhibition of ferroptosis may become a novel therapeutic strategy for the treatment of NAFLD. This review focuses on the main mechanisms behind the promotion of MAFLD/NAFLD occurrence and development by the intestinal microbiota and ferroptosis. It outlines new strategies to target the intestinal microbiota and ferroptosis to facilitate future MAFLD/NAFLD therapies.
Insights
Metabolic-associated fatty liver disease (MAFLD), replacing NAFLD, is linked to gut microbes and ferroptosis. Targeting these may offer new MAFLD/NAFLD treatments.
Area of Science:
- Hepatology and Gastroenterology
- Cellular Biology
- Microbiology
Background:
- Metabolic-associated fatty liver disease (MAFLD), formerly nonalcoholic fatty liver disease (NAFLD), is the most prevalent liver condition globally.
- MAFLD/NAFLD pathogenesis involves insulin resistance, genetic factors, and metabolic stress.
- The gut-liver axis highlights the reciprocal relationship between gut microbiota and liver health.
Purpose of the Study:
- To review the mechanisms by which gut microbiota and ferroptosis contribute to MAFLD/NAFLD development.
- To explore novel therapeutic strategies targeting the gut microbiota and ferroptosis for MAFLD/NAFLD.
Main Methods:
- Literature review focusing on the roles of intestinal microbiota and ferroptosis in MAFLD/NAFLD.
- Analysis of emerging evidence on ferroptosis as a programmed cell death pathway in liver injury.
- Examination of the gut-liver axis in the context of metabolic liver disease.
Main Results:
- Gut microbiota significantly influences the occurrence and progression of MAFLD/NAFLD.
- Ferroptosis, an iron-dependent cell death, plays a critical role in MAFLD/NAFLD pathology.
- Inhibiting ferroptosis presents a potential therapeutic avenue for MAFLD/NAFLD.
Conclusions:
- Understanding the interplay between gut microbiota and ferroptosis is crucial for MAFLD/NAFLD.
- Targeting these pathways offers promising strategies for future MAFLD/NAFLD therapies.
- The re-evaluation of gut microbiota in MAFLD/NAFLD underscores its systemic impact.
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