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MASLD Under the Microscope: How microRNAs and Microbiota Shape Hepatic Metabolic Disease Progression
Clelia Asero1,2, Maria Stella Franzè1,2, Irene Cacciola1,2
1Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy.
Abstract:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most prevalent cause of chronic liver disease worldwide. Its pathogenesis is complex and not yet fully elucidated but is commonly explained by the "multiple hit" hypothesis, which suggests that pathological behaviours interact with an unfavourable genetic background and the presence of cardiovascular comorbidities. Recent evidence has highlighted a potential role of the gut microbiota in the onset and progression of MASLD to metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC), potentially driven by epigenetic modifications mediated by microRNAs (miRNAs). MiRNAs are small, non-coding RNAs that regulate gene expression both intra- and extracellularly. Notably, emerging data suggests a bidirectional communication between the gut microbiota and the host, mediated by miRNAs via exosomes and outer membrane vesicles. The primary aim of this review is to explore the epigenetic crosstalk between the host and the gut microbiota through miRNA expression, with the goal of identifying specific pathways involved in MASLD development and natural history. A secondary objective is to evaluate the potential applications of artificial intelligence in the analysis of these complex host-microbiota interactions, to standardize the evaluation of microbiota and to create a model of the epigenetic changes in metabolic liver disease.
Insights
Metabolic dysfunction-associated steatotic liver disease (MASLD) involves gut microbiota and microRNAs (miRNAs). This review explores their epigenetic crosstalk in MASLD progression and potential AI applications for analysis.
Area of Science:
- Hepatology
- Microbiology
- Epigenetics
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease globally.
- Its complex pathogenesis involves genetic, environmental, and comorbid factors.
- The gut microbiota's role in MASLD progression to steatohepatitis (MASH) and cancer is increasingly recognized, potentially via microRNA (miRNA)-mediated epigenetic changes.
Purpose of the Study:
- To explore the epigenetic crosstalk between the host and gut microbiota via miRNA expression in MASLD.
- To identify specific pathways involved in MASLD development and progression.
- To evaluate artificial intelligence applications for analyzing host-microbiota interactions and modeling epigenetic changes in metabolic liver disease.
Main Methods:
- Literature review focusing on host-microbiota interactions, miRNA regulation, and epigenetic modifications in MASLD.
- Analysis of emerging evidence on exosome and outer membrane vesicle-mediated communication.
- Exploration of artificial intelligence tools for data analysis and modeling.
Main Results:
- Emerging data suggests bidirectional communication between gut microbiota and host via miRNAs.
- Specific miRNAs and pathways are implicated in MASLD pathogenesis and progression.
- Artificial intelligence offers potential for standardizing microbiota evaluation and modeling epigenetic changes.
Conclusions:
- Epigenetic crosstalk mediated by miRNAs plays a significant role in MASLD pathogenesis and progression.
- Understanding these host-microbiota interactions is crucial for developing novel therapeutic strategies.
- AI holds promise for advancing the study of complex interactions in metabolic liver disease.
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