Asero Clelia, Franzè Maria Stella, Cacciola Irene, Gangemi Sebastiano
Division of Medicine and Hepatology, University Hospital of Messina, 98124 Messina, Italy.
Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy.
Int J Mol Sci. 2025 Sep 4;26(17):8633. doi: 10.3390/ijms26178633.
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.
代谢功能障碍相关脂肪性肝病（MASLD）是目前全球范围内慢性肝病最常见的病因。其发病机制复杂，尚未完全阐明，但通常用“多重打击”假说来解释，该假说认为病理行为与不利的遗传背景以及心血管合并症的存在相互作用。最近的证据突出了肠道微生物群在MASLD发展为代谢功能障碍相关脂肪性肝炎（MASH）和肝细胞癌（HCC）的起始和进展中的潜在作用，这可能由微小RNA（miRNA）介导的表观遗传修饰驱动。miRNA是小的非编码RNA，可在细胞内和细胞外调节基因表达。值得注意的是，新出现的数据表明肠道微生物群与宿主之间存在双向通讯，由miRNA通过外泌体和外膜囊泡介导。本综述的主要目的是通过miRNA表达探索宿主与肠道微生物群之间的表观遗传串扰，以确定参与MASLD发展和自然史的特定途径。第二个目标是评估人工智能在分析这些复杂的宿主-微生物群相互作用中的潜在应用，以规范微生物群的评估并创建代谢性肝病表观遗传变化模型。
