Molecular mechanisms of gut microbiota dysbiosis in driving metabolic dysfunction-associated fatty liver disease via the gut-liver axis
DING Yao
CHENG Jie
XIONG Yujing
ZHAO Haitao
WANG Jingjie
Abstract：Metabolic dysfunction-associated fatty liver disease(MAFLD)has emerged as the most prevalent chronic liver disease worldwide.The pathological transition from simple steatosis to steatohepatitis and subsequent liver fibrosis is a key determinant of prognosis,with persistent hepatic inflammation serving as the core driver of this detrimental progression.Currently,no specific pharmacotherapies are approved for the steatohepatitis stage,which has directed research focus toward the gut-liver axis.This review systematically elucidates the molecular pathways by which gut dysbiosis drives hepatic inflammation in MAFLD via the gut-liver axis and discusses corresponding therapeutic strategies.Gut barrier dysfunction leads to continuous translocation of pathogen-associated molecular patterns,such as lipopolysaccharide,into the liver through the portal vein.This activates the TLR4/NF-κB pathway in Kupffer cells,inducing the release of proinflammatory cytokines,including TNF-α and IL-6.Concomitant shifts in gut microbial metabolic profiles result in reduced production of protective metabolites(e.g.,short-chain fatty acids and secondary bile acids)and accumulation of pathogenic metabolites such as trimethylamine-N-oxide,thereby compromising the host's anti-inflammatory capacity.Moreover,the gut mycobiota is significantly enriched in MAFLD patients,promoting IL-17 secretion and elevating the Th17/Treg ratio,which in turn activates hepatic stellate cells and exacerbates both inflammation and fibrosis.Activation of the NLRP3 inflammasome further amplifies the IL-1β-mediated inflammatory cascade.Based on these mechanisms,therapeutic strategies include probiotics,fecal microbiota transplantation(FMT),dietary interventions to restore gut microbial homeostasis,as well as pharmacological agents targeting the FXR,NLRP3,and IL-17 pathways.However,FMT carries a risk of bacteremia in patients with an impaired intestinal barrier,and standardization of donor selection and FMT protocols remains to be established.Future studies should employ single-cell transcriptomics and integrative multi-omics analyses to clarify causal links between microbial signals and inflammatory pathways,thereby providing a rationale for inflammatory stratification and precision intervention in MAFLD.
Keywords：metabolic dysfunction-associated fatty liver diseasegut microbiotagut-liver axishepatic inflammationlipopolysaccharideToll-like receptor 4nuclear factor kappa BNLRP3 inflammasome
Publication Date：2026-06-30
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：6( 909-913,921 )