Abstract:
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disorder characterized by
hepatic steatosis, inflammation, and fibrosis, with a growing body of evidence highlighting the
critical roles of gut microbiota and microRNAs (miRNAs) in its pathogenesis. The gut-liver axis
serves as a key regulatory network, where microbiota-derived metabolites, including short-chain
fatty acids (SCFAs), bile acids, and lipopolysaccharides (LPS), influence hepatic lipid
metabolism and immune responses. Concurrently, miRNAs regulate gene expression in the liver
and intestines, modulating lipid homeostasis, inflammation, and fibrosis. Notably, miR-122,
miR-34a, and miR-21 play significant roles in disease progression. Recent studies suggest a
bidirectional relationship between microbiota and miRNAs, where microbial metabolites alter
miRNA expression, and host-derived miRNAs shape microbiota composition and gut-liver
signaling. Dysbiosis-induced changes in miRNA profiles contribute to increased intestinal
permeability, endotoxemia, and chronic hepatic inflammation, exacerbating NAFLD
progression. Understanding these intricate molecular interactions is essential for elucidating
NAFLD pathophysiology. This review explores the complex interplay between gut microbiota
and miRNAs in NAFLD, providing insights into the mechanisms underlying disease
development and progression. A deeper understanding of these relationships may enhance our
comprehension of NAFLD as a systemic disorder involving the gut-liver axis.
