Immunological interactions between the gut microbiome and the liver in non-alcoholic fatty liver disease: mechanisms and potential therapeutic targets

Non-alcoholic fatty liver disease (NAFLD) is closely tied to lifestyle factors like diet and obesity. The gut microbiome’s influence on immune pathways and dysregulations is increasingly recognized in NAFLD. We explore how the microbiome impacts local and systemic immune responses contributing to NAFLD’s development, discussing mechanisms and novel interventions like probiotics. Our review identifies immune pathways and microorganisms regulating lipid/glucose metabolism, liver inflammation/fibrosis. TLR-4, activated by lipopolysaccharides, is a key pathway producing pro-inflammatory cytokines, worsening inflammation. Endotoxin-producing strains (Enterobacter cloacae B29, Escherichia coli PY102, Klebsiella pneumoniae A7) induce NAFLD animal models via TLR4-dependent response. These bacteria may contribute to NAFLD via immune/non-immune means. The gut microbiome significantly modulates immune-inflammatory responses in NAFLD and other liver diseases. This review stimulates further research into gut microbiome-liver interactions and innovative treatments for this prevalent condition.